Clinical Manifestations Of Celiac Disease Research Articles

Neuropsychiatric manifestation of celiac disease: A case-control study in North India

Background: Celiac disease (CD) is an immune-mediated disease dependent on gluten. Prevalence of CD is about 1% and beside gastrointestinal complaints, neuropsychiatric symptoms may represent an atypical feature of CD. Some studies suggest that a gluten-free diet is effective in treating them. Settings and Design: This case-control study of 49 cases was done during the period of January to March 2013. Aim: To know the spectrum of psychiatric manifestations and cognitive functions in children with CD. Materials and Methods: We took 49 diagnosed cases of CD (based on the demonstration of IgA tissue transglutaminase antibodies and duodenal biopsy) and compared with demographically matched control group ( n = 50) on Seguin Form Board Test for cognitive functions and Behavioral Summarized Evaluation-Revised scale for assessment of psychiatric and behavior disturbances. All possible psychiatric diagnosis was made on the basis of International Statistical Classification of Disease and Related Health Problems-Tenth Revision criteria. Statistical Analysis: Statistical analyses were done by using Chi-square test and two-tailed P -values. Results: Neuropsychiatric manifestations were seen in 29% of cases as against 4% of controls which was statistically significant ( P =0.001). Only four cases and 1 control fount to be mild mental retardation ( P = 0.16). Autism, dyslexia, developmental delay, disruptive behavior disorder, and tic disorder present in cases were not found. Conclusion: Clinical manifestations of CD vary from typical malabsorption syndrome to neuropsychiatric manifestations. Those psychiatric patients who are not responding to standard pharmacological modalities, a diagnosis of CD should be taken into consideration. Only behavioral problem can be the sole clinical manifestation of CD.

Serological tests for celiac disease in Moroccan patients with type 1 diabetes

La maladie cœliaque (MC) est l'une des maladies auto-immunes les plus fréquemment associées au diabète de type 1 (DT1). La prévalence de MC dans DT1 varie de 3 à 6%. La présentation clinique de MC dans DT1 est classé comme asymptomatiques dans environ la moitié des cas. L'objectif de notre étude est de déterminer la fréquence des auto-anticorps anti-transglutaminase tissulaire (AtTG) et anti-gliadines (AAG) chez les patients diabétiques de type 1 dans le but de recommander une éventuelle biopsie jéjunale et d'instaurer un régime sans gluten précocement avant l'installation des signes cliniques et des complications de la maladie cœliaque. Les sujets inclus dans cette étude sont des patients atteints de DT1 non traités pour la MC et qui ne présentent pas de signes en faveur de cette pathologie. La détection des AtTG de classe IgG et IgA et AAG classe IgG et IgA a été réalisée par technologie Luminex. Nous avons inclus 31 patients. Il s'agit de 16 hommes et 15 femmes. Les AAG de classe IgA étaient positifs chez 4(13%) patients et chez 7(22,5%) patients pour les IgG. Les AtTG de classe IgA étaient positifs chez 3(10%) patients et chez une patiente (3%) pour les IgG. Dans notre étude l'association du diabète type 1 et des marqueurs biologiques de la MC n'est pas rare d'où l'intérêt de son dépistage systématique chez des diabétiques de type 1. Le diagnostic de cette forme atypique et silencieuse de la MC est important compte tenu du risque de complications sérieuses à type de malabsorption et de cancers digestifs.

The clinical manifestations of celiac disease may present at any age: A rare case report

A case report of a 87-year-old woman developing celiac disease has been discussed. The patient complained of irregularbowel habit, abdominal pain and mild weight loss at the walk-in clinic. Having symptoms fulfilling the ROME III criteria,fibromyalgia and osteopenia were the co-existing syndromes. The laboratory findings showed signs of anemia. Positiveserological tests and duodenal biopsies confirmed the diagnosis of celiac disease. She was treated with gluten-free diet.Accordingly her symptoms relieved and her findings improved.

Extraintestinal manifestations of coeliac disease.

Coeliac disease is a common disorder that can arise at any age and typically presents with a broad spectrum of symptoms. The disease is thought to be underdiagnosed, in part owing to the fact that coeliac disease is often characterized by associated conditions and extraintestinal manifestations that can misdirect and impede diagnosis. Some of these manifestations are direct consequences of autoimmunity, such as dermatitis herpetiformis or gluten ataxia, whereas others are indirectly related to inflammation and/or malabsorption including anaemia, osteoporosis, short stature and delayed puberty. Any organ from the central nervous system to joints, liver or teeth can be affected. In some cases, extraintestinal symptoms are the only clinical manifestations of coeliac disease or occur in conjunction with diarrhoea and malabsorptive symptoms. An increased awareness among medical practitioners of the variety of extraintestinal manifestations of coeliac disease is essential to improve diagnosis and treatment.

Celiac Disease: A Disease With Varied Manifestations in Adults in India

BackgroundIn India incidence of celiac disease is rising and more prevalent in the Northern part of the country, the so-called “coeliac belt”, a finding that is at least partially explained by the wheat-rice shift from the North to the South.Aim and MethodsThe aim of the present study was to determine clinical manifestations of celiac disease in western India. In retrospective analysis of prospectively maintained data at single tertiary health center, Patients diagnosed with CD based on modified ESPGHAN criteria were evaluated for clinical features, serology and histology of endoscopic duodenal biopsy.ResultA total of 75 patients diagnosed by modified ESPGHAN criteria (46 females, mean age 36±15 years) had positive serology- IgA Anti Endomyceal antibody (n-72), IgA Anti tTG antibody (n-3) and 6%, 28%, 3%, 62% patients had Marsh stage 0, 1, 2,and 3 respectively. Sixty-five percent of patients presented with typical diarrheal disease. One or more associated diseases were noted in 27 (36%) patients and most common being autoimmune disease (16%) (Hypothyroidism, grave’s disease, autoimmune hepatitis, DM type 1, Rheumatoid arthritis) followed by neurological conditions (9%) (Epilepsy, depression, schizophrenia, ataxia, migraine). Most common atypical manifestations were anaemia (76%) followed by elevated transaminases (39%), osteopenia (25%), neurological (4%) and infertility (1%).ConclusionCeliac disease is also common in western India and atypical manifestations and associated conditions should be actively screened in all CD patients. BackgroundIn India incidence of celiac disease is rising and more prevalent in the Northern part of the country, the so-called “coeliac belt”, a finding that is at least partially explained by the wheat-rice shift from the North to the South. In India incidence of celiac disease is rising and more prevalent in the Northern part of the country, the so-called “coeliac belt”, a finding that is at least partially explained by the wheat-rice shift from the North to the South. Aim and MethodsThe aim of the present study was to determine clinical manifestations of celiac disease in western India. In retrospective analysis of prospectively maintained data at single tertiary health center, Patients diagnosed with CD based on modified ESPGHAN criteria were evaluated for clinical features, serology and histology of endoscopic duodenal biopsy. The aim of the present study was to determine clinical manifestations of celiac disease in western India. In retrospective analysis of prospectively maintained data at single tertiary health center, Patients diagnosed with CD based on modified ESPGHAN criteria were evaluated for clinical features, serology and histology of endoscopic duodenal biopsy. ResultA total of 75 patients diagnosed by modified ESPGHAN criteria (46 females, mean age 36±15 years) had positive serology- IgA Anti Endomyceal antibody (n-72), IgA Anti tTG antibody (n-3) and 6%, 28%, 3%, 62% patients had Marsh stage 0, 1, 2,and 3 respectively. Sixty-five percent of patients presented with typical diarrheal disease. One or more associated diseases were noted in 27 (36%) patients and most common being autoimmune disease (16%) (Hypothyroidism, grave’s disease, autoimmune hepatitis, DM type 1, Rheumatoid arthritis) followed by neurological conditions (9%) (Epilepsy, depression, schizophrenia, ataxia, migraine). Most common atypical manifestations were anaemia (76%) followed by elevated transaminases (39%), osteopenia (25%), neurological (4%) and infertility (1%). A total of 75 patients diagnosed by modified ESPGHAN criteria (46 females, mean age 36±15 years) had positive serology- IgA Anti Endomyceal antibody (n-72), IgA Anti tTG antibody (n-3) and 6%, 28%, 3%, 62% patients had Marsh stage 0, 1, 2,and 3 respectively. Sixty-five percent of patients presented with typical diarrheal disease. One or more associated diseases were noted in 27 (36%) patients and most common being autoimmune disease (16%) (Hypothyroidism, grave’s disease, autoimmune hepatitis, DM type 1, Rheumatoid arthritis) followed by neurological conditions (9%) (Epilepsy, depression, schizophrenia, ataxia, migraine). Most common atypical manifestations were anaemia (76%) followed by elevated transaminases (39%), osteopenia (25%), neurological (4%) and infertility (1%). ConclusionCeliac disease is also common in western India and atypical manifestations and associated conditions should be actively screened in all CD patients. Celiac disease is also common in western India and atypical manifestations and associated conditions should be actively screened in all CD patients.

Diagnostic Challenges in Celiac Disease

1. The most important challenge in diagnosis of celiac disease is not-performing the diagnostic tests in suspected persons. Because of multi-organ damage and multiple manifestations of disease, diagnosis of celiac disease may be delayed. It seems general physicians should be aware about uncommon presentations of disease and indications of celiac tests. 2. The second most important challenge is in patients with suspected disease but negative serologic tests. In these cases evaluating of HLA can be useful. 3. The third challenge is in cases with positive serologic tests but negative histopathological findings. There may be false positive serologic response or consumption of gluten before testing. We recommend introduction of gluten for at least 3 mo and re- endoscopy and if diagnosis is equivocal HLA-typing for DQ8 and DQ2 should be done. 4. The forth challenge is about performing endoscopy. Based on guideline from ESPGHAN if there are typical clinical manifestations of celiac disease, Anti-TTG more than ten times UPN, positive Anti-EMA and HLA DQ2, performing endoscopy may not be necessary, but many physicians don’t agree with this idea. 5. In people who are genetically predisposed to celiac disease antibody levels may be fluctuating thus endoscopy with biopsy should be done in these patients. 6. In children lower than 2years, Anti- TTG and Anti –EMA have low sensitivity. we recommend Anti-TTG and Anti-DGP in these patients. 7. Resolution of symptoms after gluten free diet is not necessarily a feature of celiac disease. This condition may be seen in patients with IBS or non-celiac gluten sensitivity.

Second Gluten and Food Related Disorders Conference. Worcester, UK. December 6-7 2012

Second Gluten and Food Related Disorders Conference. Worcester, UK. December 6-7 2012

Gluten-dependent Intestinal Autoimmune Response

Celiac disease is a multi-systemic autoimmune disease of the small bowel induced by gluten in genetically predisposed subjects. Highly specific and gluten-dependent production of auto-antibodies targeting self-proteins of the transglutaminase family occurs in the intestinal mucosa. These anti-transglutaminase antibodies are found deposited in intestinal and extra-intestinal tissue where they might exert biological effects, together with the intestinal mucosal gliadin-specific T lymphocytes. We conducted a brief review on antitransglutaminase antibodies effects, discussing their roles in the pathogenesis of several clinical manifestations of celiac disease.

442 Coincidence of Celiac Disease and Gluten Allergy

BackgroundThe type I or IV of hypersensitivity reactions according to Gell and Coombs classification may be responsible for clinical symptoms observed after ingestion of gluten - containing products. The mechanisms of these reactions are either IgE-dependent or IgE-independent. Celiac disease based on IgE-independent mechanism is classified as gluten hypersensitivity. Clinical manifestation of celiac disease and gluten allergy is often similar. Correct diagnosis of this disease is particularly important due to the different long-term therapeutic procedures. We would like to asses of the incidence of celiac disease in children with gluten allergy.MethodsThe study involved 50 children with abdominal pain, chronic diarrhea, recurrent respiratory and ears inflammation and skin lesions - patients of the Immunological and Gastroenterology Outpatient Clinic of Institute of Mother and Child. The allergy to gluten was confirmed on the basis of positive peripheral blood lymphocytes blast transformation test and detection of allergen-specific IgE antibodies to gluten (f79). In all children plasma concentration of immunoglobulin classes A, G M and IgA or IgG antibodies against tissue transglutaminase (tTGA) were measured.ResultsIn children on the study group the type IV of hypersensitivity reaction to gluten was diagnosed. In 3 children specific IgE antibodies to gluten was also confirmed (f79 - I type hypersensitivity). Anti-tissue transglutaminase antibodies both IgA and IgG were detected in 2 children in whom the concentration of IgA and IgG in serum remained within normal range for age. In these children celiac disease was confirmed by jejunal biopsy.ConclusionsThe predominant frequency of type IV of hypersensitivity reactions in children in response to the gluten antigen should be taken into account in diagnosis of food allergy.In children diagnosed with gluten allergy the test for celiac disease should be performed.

Coeliac disease: clinical features in adult populations

coeliac disease (CD) is a chronic disease of the small intestine, which is caused by gluten intolerance, producing malabsorption of nutrients and vitamins. Clinical manifestations of CD in adults are highly variable, including intestinal and extra-intestinal symptoms. The disease may also occur in individuals who are asymptomatic. our objective is to describe the incidence and clinical manifestations of CD in adults. a retrospective study was carried out in patients diagnosed of CD between January 1990 and December 2008. Diagnosis was based on serologic tests and duodenal biopsy, which were compatible with CD in all of them. sixty eight adult patients were diagnosed of CD in this period. Mean age was 33 (18-65) years and 50 (74%) were women. The clinical manifestations were diarrhoea in 38 (55%), abdominal pain in 27 (40%), loss of weight in 15 (22%), dyspepsia in 13 (19%). Analytical results showed a slight increase of transaminases in 26 (38%), ferropenic anaemia in 33 (48.5%) cases, sub-clinical hypothyroidism in 3 (4.5%) patients, and folic acid deficiency in 16 (23.5%) cases. Almost all patients were diagnosed between 2000 and 2008: 60 (87%). Population-based incidence of CD in adults had increased from 0.7-2/100,000 per year in the nineties to 3.5-10.3/100,000 in the last years. CD can appear at any age and with a wide manifestation spectrum, which can be atypical in some cases. Patients with ferropenic anaemia and a negative response to treatment or those with an unexplained increase in transaminases should be screening for CD. Atypical manifestations and low suspect index can delay diagnosis even during years. There is a marked increase in the incidence-rates of CD in adults over time.

The Assessment of Autoimmunological Status and Prevalence of Different Forms of Celiac Disease among Children with Type 1 Diabetes Mellitus and Celiac Disease

This study aims to assess the autoimmunological status and forms of celiac disease (CD) among children with type 1 diabetes mellitus (T1DM). The study group comprises 27 patients at the mean age of 12.30 years (±SD 3.12). The measurement of the level of diabetes-specific antibodies and organ-specific antibodies was gained at the T1DM-onset and repeated annually. The following risk factors influencing time of CD diagnosis were analyzed: age, sex, T1DM duration, autoantibodies, and HLA-haplotype. The prevalence of antibodies was GADA-74%, IAA-63%, IA2A-67%, ATA-11%, and ATG-4%. The intestinal biopsy revealed in 19% no changes and in 77% stage 3 (Marsh scale). In most cases, no clinical manifestation of CD was observed. The diagnosis of Hashimoto's disease was made twice. The negative correlation between the age at T1DM-onset and the interval between onset of T1DM and CD (r = −0.35, p < .05) was noted. The high-comorbidity ratio of CD and thyroiditis with T1DM demands regular screening tests especially in the first years after T1DM-onset.

Anemia in celiac disease is multifactorial in etiology

Anemia in celiac disease (CD) has been attributed to nutritional deficiencies; however, the clinical manifestations of CD have changed with nongastrointestinal presentations predominating. We collected hematologic parameters from a cohort of patients seen at a tertiary care center for CD to assess the characteristics of anemia in this population. Hematological parameters measured <or=3 months of diagnosis and degree of villous atrophy from 405 patients diagnosed >1995 was analyzed. Ferritin levels were compared with population controls (NHANES III). Iron deficiency was common, occurring in 33% of men and 19% of women (P < 0.001). Folate deficiency was seen in approximately 12% of the total sample and B12 deficiency in approximately 5%. Anemia was present in approximately 20% of the cohort. Among the anemic patients, ferritin was less than the 10th percentile in 45%, between the 10th and 50th percentile in 39% and greater than the 50th percentile in 13%. Ferritin > 50th percentile was more common in anemic men (24%) than in anemic women (9%; P > 0.20). Macrocytic anemia with concurrent B12 or folate deficiency was rare (3%). Elevated ESR was observed in patients with ferritin < 10th percentile and >50th. A gluten-free diet resulted in increased serum ferritin in iron-deficient patients, and decreased ferritin levels in those with high ferritin (r(2) = 0.46, P < 0.001). Although anemia is still a common presentation of celiac disease, nutritional deficiencies alone do not explain this phenomenon in all cases; inflammation appears to contribute as evidenced by the presence of anemia of chronic disease in some individuals.

Prevalence of Silent Celiac Disease in Patients with Dyspepsia

Celiac disease (CD) has become more common than in the past, although it frequently remains undetected for long periods of time. One reason for this is failure by health care professionals to recognize the variable clinical manifestations of CD and to perform the appropriate tests to make the diagnosis. Although dyspepsia may be part of a clinical spectrum in CD patients, there are scarce data about its prevalence in silent CD. We aimed to determine the prevalence of CD in otherwise healthy dyspeptic patients by means of serologic screening followed by endoscopic biopsies if appropriate. Anti-endomysium antibody assay was positive in 3 of 196 patients. All 3 were female, ages ranged from 19-52 years (mean +/- SD age, 36 +/- 16 years). Duodenal biopsies were compatible with CD in all, whereas abnormal endoscopic findings were noted in 2. Therefore, a 1.5% prevalence of CD was observed in this study group. The odds ratio for CD was 2.57 (95% confidence interval) in comparison with the general population. CD should be kept in mind as a cause of dyspepsia during clinical activities. The association between these 2 conditions is, at most, weak, but a gluten-free diet may still bring symptomatic relief for dyspeptic symptoms in CD. During endoscopic examination for dyspepsia, if indicated, endoscopists should carefully inspect the duodenum for CD findings. Although routine serologic screening can not be recommended, it may be appropriate for the patients with refractory dyspepsia, especially females.

Management of celiac disease in childhood and adolescence: Unique challenges and strategies

Celiac disease (CD) is a common condition that occurs in genetically predisposed individuals when they ingest products containing wheat, barley, or rye. It produces an autoimmune-mediated enteropathy with characteristic histologic features on small intestinal mucosal biopsy. The clinical manifestations of CD are highly variable and initially may be unrelated to the gastrointestinal system. The condition is also strongly associated with other autoimmune and nonautoimmune conditions. Physicians caring for children and adolescents are challenged with identifying those who might have CD and require referral for definitive testing, recognizing the potential pitfalls in the diagnostic work-up of the pediatric patient, and providing ongoing care for those with a positive diagnosis. Confirmation of the diagnosis mandates that the individual be placed on a strict gluten-free diet (GFD) for life, as this is the only treatment currently available for CD. This article will discuss the immunopathogenesis, epidemiology, and clinical manifestations of CD and will outline a strategy of active case-finding using serological tests to identify those who require an intestinal biopsy for definitive diagnosis. The need for lifelong treatment by means of a GFD and for continued follow-up of children and adolescents after diagnosis is emphasized.

Differing Clinical Manifestations of Celiac Disease Transmitted by Bone Marrow Transplantation

Differing Clinical Manifestations of Celiac Disease Transmitted by Bone Marrow Transplantation

Celiac disease in South-West of Iran

Celiac disease is characterized by life-long gluten intolerance. Clinical features of patients with celiac disease are variable. Studies about the prevalence of celiac disease in our country are scarce and there is no study on the prevalence of celiac disease in southern Iran. In the current study, clinical, laboratory and histo-logical features of 52 patients with celiac disease were evaluated. In a cross sectional study we retrospectively studied the characteristics of 52 celiac patients at Ahwaz JundiShapour University Hospitals (AJSUH) from November 1, 1999 to 1st Sep 2004. Intestinal biopsy and serum antigliadin and anti-endomysium antibodies were used for the diagnosis of patients. Mucosal lesions were classified according to the criteria of Marsh. Antigliadin antibodies were measured with a commercial enzyme-linked immunosorbent assay. Anti-endomysium antibodies were analyzed by indirect immunofluorescence with the use of a section of monkey esophagus. Routine hematological and biochemical analyses and measurement of immunoglobulin levels were undertaken. Male: female ratio was 1.08. The mean +/- SD patient age was 21 +/- 4.5 years (range 10-70 years) and the most common symptoms were diarrhea and weight loss (78.8%) followed by fatigue (73.1%), pallor (65.4%), anorexia (40.4%), abdominal distention (32.7%), and failure to thrive (23.1%). Diarrhea and weight loss and fatigue were the most common findings. Iron deficiency anemia was found in 63.2% of patients and this became normal after adoption of a gluten-free diet in all patients. Immunoglobulin A, IgG antigliadin antibodies and IgA anti-endomysium antibodies were found in 33 and 48 cases, 78.8% and 85.4% of patients, respectively. Biopsy of the small intestine revealed that 90.4% of patients had typical lesions according to the Marsh classification. Although classical presentation was seen in most of the patients, atypical clinical manifestations of celiac disease should be kept in mind. In particular, patients with uncommon findings, such as short stature, and iron-deficiency anemia, should be screened for celiac disease. Further epidemiological studies in our area in the general population and in high risk groups seem to be indicated.

Clinical presentation of celiac disease in the pediatric population

Celiac disease (CD) is an immune-mediated enteropathy triggered by the ingestion of gluten-containing grains (including wheat, rye, and barley) in genetically susceptible individuals. CD is associated with HLA molecules DQ2 (90%-95%) and DQ8 (5%-10%), and in the continued presence of gluten the disease is self-perpetuating. CD is one of the most common lifelong disorders worldwide and is characterized by a variety of clinical presentations. These include the typical malabsorption syndrome (classic symptoms) and a spectrum of symptoms potentially affecting any organ or body system (nonclassic symptoms). Because CD often is atypical or even clinically silent, many cases go undiagnosed and are exposed to the risk of long-term complications. There is growing interest in the social aspects of CD because the burden of illness related to this condition is doubtless higher than previously thought.

Intestinal involvement is not sufficient to explain hypertransaminasemia in celiac disease?

Chronic unexplained hypertransaminasemia is an isolated clinical manifestation of celiac disease (CD) and lacks of a clear physiopathological explanation. Since CD and tropical sprue (TS) have similar intestinal functional and histological pattern of injury and that an increased inflammatory response has been reported to occur in patients with irritable bowel syndrome (IBS), liver involvement might be expected to occur either in TS or IBS. However, according to author's prior observations, the frequency of hypertransaminasemia is significantly higher in CD than in TS and IBS-diarrhea predominant patients (IBS-D). Thus, based on current knowledge, intestinal mucosal damage, increased intestinal permeability and/or an active intestinal inflammatory response do not completely explain liver damage in CD. We hypothesize that other factors, unique to CD not present in TS or IBS-D, like gluten toxicity and the presence of tissular transglutaminase (tTG) an auto-antigen with pro-inflammatory and remodeling properties, act in addition to intestinal mucosal injury and account to hypertransaminasemia in CD. Further research focusing on the mechanisms of gluten and tTG hepatic toxicity, and/or the characterization of the expression, secretion and enteral-hepatic transport of certain pro-inflammatory cytokines is needed, to understand the possible links between intestinal and liver disorders seen in CD.

Serological screening for undiagnosed coeliac disease in male adolescents in Lower Austria

There is a wide variation in the clinical manifestations of coeliac disease (CD). Several recent screening investigations have attempted to determine the true prevalence of CD and rates of undiagnosed CD between 1:22 [3] and 1:1170 [5] have been reported. As there are no data on the prevalence of undiagnosed CD in Austria, the aim of our study was to establish the frequency of positive tissue transglutaminase antibodies (tTGA) in a cohort of male adolescents. During the compulsory conscript medical examination (June 2001–July 2002), an additional blood sample C. Edlinger-Horvat AE D. Fidler AE W.-D. Huber AE B. Rami G. Granditsch AE E. Schober (&) Department of Paediatrics, University Children’s Hospital, Waehringer Guertel 18–20, 1090 Vienna, Austria E-mail: edith.Schober@akh-wien.ac.at Tel.: +43-1-404003232 Fax: +43-1-40400 3238

Coeliac disease in Middle Eastern countries: a challenge for the evolutionary history of this complex disorder?

About 10,000 years ago domestication and farming of wheat and other cereals developed in the ‘Fertile Crescent’, an area including modern Turkey, Iraq and Iran. Agriculture then slowly spread from Middle East to Europe. Coeliac disease is the permanent intolerance to dietary gluten, the major protein component of wheat. It has been until relatively recently hypothesised that wheat consumption exerted a negative selective pressure on genes predisposing to coeliac disease, eventually leading to higher coeliac disease frequency in Northeastern Europe because of lack of exposure to cereals. This theory is at variance with recent studies showing that coeliac disease is as common in Middle Eastern countries as in Europe. High prevalence of coeliac disease has been found in Iran, in both the general population and at-risk groups, e.g. patients with irritable bowel syndrome or type 1 diabetes. Clinical manifestations of coeliac disease vary markedly with the age of the patient, the duration and the extent of disease. Clinical studies showed that presentation with non-specific symptoms or no symptoms is as common in the Middle East as in Europe. Wheat represented a major component of the Iranian diet for many centuries and it may be argued that the continuous and high level of exposure to wheat proteins has induced some degree of immune tolerance, leading to milder symptoms that may be misdiagnosed as irritable bowel syndrome or unexplained gastrointestinal disorders. The gluten-free diet represents a real challenge to both patients and clinicians in this area. This is particularly difficult in the absence of any supply for gluten-free diet in Middle Eastern countries.