Classical Celiac Disease Research Articles

Prevalence and Associated Morbidity of Undiagnosed Celiac Disease in Young Adults

Purpose: Celiac Disease (CD) is an autoimmune disorder of the proximal small intestine which induces inflammatory cascades that damage the absorptive villous architecture of the small intestine. Hallmark symptoms of the resulting malabsorption are diarrhea, steatorrhea, and flatulence along with malabsorption consequences including growth failure, anemia, fracture, and weight loss. In addition, the autoimmune properties of CD have been associated with hepatitis, diabetes, thyroid disorders, and many other autoimmune conditions. CD is likely common, but the majority of patients are undiagnosed at any point in time. It is not known whether these individuals suffer any manifestations from silent or undiagnosed CD. Prior studies using the Rochester Epidemiology Project have identified all diagnosed cases of CD in Olmsted County, MN residents. Methods: In the present study, we estimate prevalence of undiagnosed CD in a convenience sample obtained from the ˜67,000 Olmsted County residents' ages of 18-50. An initial screening tissue transglutaminase IgA (tTG-IgA) assay, with confirmation via endomysial antibody immunofluorescence was done on waste blood samples from 19,671 unique individuals. Subjects were categorized as positive (cases) or negative according to their serology result. A 1:2 matched (on age and gender) set of controls was obtained from those with negative serology. The risk of various co-morbidities at or prior to the serum draw in undiagnosed sero-positive cases was compared to matched controls using conditional logistic regression. Odds ratios (OR) with 95% confidence intervals (CI) are reported as a measure of the strength of associations between co-morbidity and serology status. Results: The prevalence of undiagnosed CD in the cohort of Olmsted County residents age 18-50 was 1.1% (95% CI=1.0%-1.3%) which reflects the estimated prevalence of undiagnosed celiac disease in the general population in this age range. None of the hallmark symptoms and consequences of classic CD including diarrhea, anemia, and fracture were increased in the sero-positive subjects. However, the sample of Olmsted County residents with undiagnosed CD were found to have increased odds for chronic fatigue (OR=1.90; 95% CI, 1.1-3.4; p=0.031) and hypothyroidism (OR=2.13; 95% CI, 1.1-4.2; p=0.033) among the ˜80 co-morbidities assessed. Conclusion: Overall, this preliminary analysis reveals no consistent constellation of patient co-morbidities associated with sero-positive status in a community sample of Olmsted County residents age 18-50. Undiagnosed CD in this population-based cohort appears largely silent.

Celiac Disease: Presentation of 109 Children

PurposeThe clinical features of patients with celiac disease (CD) are variable. In the present study, clinical and laboratory features of 109 patients with CD were retrospectively evaluated.Materials and MethodsIn all cases, diagnosis of CD was made by European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) criteria and clinical and laboratory findings, including hematological and biochemical analyses, immunoglobulin levels, autoantibodies [antinucler antibody (ANA), antidouble stranded DNA (dsDNA), antimitochondrial antibody (AMA), anti-smooth muscle antibody (ASMA), liver kidney antibody (LKM-1), anti thyroid peroxidase (TPO), anti thyroglobulin (Tg)], bone mineral density (BMD), and electroencephalogram were evaluated. The type of CD was recorded.ResultsOf 109 patients with CD, 66 (60.6%) were classical type, 41 (37.6%) were atypical type and 2 (1.8%) were silent type. The mean age was 8.81 ± 4.63 years and the most common symptom was diarrhea (53.2%) followed by failure to thrive, short stature, and abdominal pain. Paleness (40.4%), underweight (34.8%), and short stature (31.2%) were the most common findings. Iron deficinecy anemia (81.6%), zinc deficiency (64.1%), prolonged prothrombin time (35.8%), and elevated transaminase levels (24.7%) were the most common laboratory findings. Eight percent of patients had at least 1 autoantibody, and 28 of 52 patients had low BMD. Four of 38 patients had abnormalty in electroencephalograms. The prevalance of selective immunoglobulin (Ig) A deficiency was 9.1%. Histocompatibility antigen HLA-DQ and/or DQ8 genotypes were found in 91% of patients. Abdominal distention, iron deficiency, prolonged prothrombine time, hypoalbuminemia, and elevated transaminase levels were more significantly frequent in the classical type than atypical type (p < 0.005).ConclusionAlthough classical CD was seen in most patients in the present study, clinical variability of the condition should be kept in mind.

Effect of gluten-free diet on the growth and nutritional status of children with coeliac disease

Gluten-free diet (GFD) presents the basis of coeliac disease (CD) treatment. If strictly applied, the disorders of the small bowel mucosa and other disease signs rapidly resolve. The goal of the study was to evaluate the effect of GFD on the growth and nutritional status of children with the classical form of CD. In addition, we analyzed the differences between these parameters with the duration and the patients' compliance with GFD. The study goals were achieved on a sample of 90 children, 56 female and 34 male, aged 0.5-7.5 (1.53 +/- 1.05) years, with the classic CD diagnosed on the basis of typical pathohistological findings of the small bowel mucosa and clinical recovery of patients on GFD. The duration of the patients' follow-up was 1.08-8.75 (3.03 +/- 1.14) years, i.e. until the age of 2.5-15 (4.59 +/- 1.78) years. The initial and control values of body height (BH) in relation to matched values for age and gender were expressed in percentiles, while the deviation in body weight (BW) for the matched values of height and gender was expressed in percentages. The referent haemoglobin (Hb) rate in blood, as a laboratory indicator of nutritional status in children aged up to 5 years was > or = 110 g/L, and for those aged above 5 years it was > or = 115 g/L Compliance with GFD was based on the pathohistological findings of the small bowel mucosa or determination of tissue transglutaminase. Over the studied period, the effect of GFD was highly significant, both on the increase of BH percentiles (37.62 +/- 26.26 vs. 57.22 +/- 25.29; p < 0.001), and on the decrease of BW deficit 11.58 +/- 10.80 vs. 0.89 +/- 8.194; p < 0.001). After the treatment period, none of the children showed slowed growth rate or BW deficit above 20%, while BW deviation ranging between 10-20% in relation to the referent values was registered in 17 (18.19%) and the excess of over 20% in 2 patients. In 86 (95.56%) patients, control Hb values in blood were normal, while mild anaemia was registered in 4 patients, all compliant with GFD. The difference between the compliant and non-compliant patients with GFD was not detected either in BH percentiles (p = 0.586) or in BW percentage deviation as compared to standard values (p = 0.516) or in blood Hb values (p = 0.445). In addition, differences between the children on GFD lasting over and below 3 years were not detected either in BH percentiles (p = 0.915) or in BW deviation percentages in relation to the ideal rate (p = 0.476). GFD applied for 1-3 years has a highly significant effect on the growth rate and nutritional status of children with the classical form of CD. Significant differences in these parameters of the disease were not detected between strictly compliant and non-compliant patients on GFD.

Complications in Celiac Disease Under Gluten-Free Diet

We assessed the onset of malignant and nonmalignant complications in a cohort of celiac disease (CD) patients under gluten-free diet (GFD). Five hundred and forty-nine CD patients were retrospectively assessed. Two hundred and fifty-one (45.7%) showed classical, 262 (47.7%) subclinical, and 36 (6.6%) silent form of CD at the time of the diagnosis. The mean time under GFD was 7.13 years (range 1-15 years). Out of 549 patients, 381 (69.4%) were fully compliant, 112/549 (20.4%) reported less than one dietary transgression/month, and 56/549 (10.2%) reported at least one dietary transgression/month. Out of 549 patients, 18 (3.3%) patients developed complications under GFD (seven malignant and 11 nonmalignant complications). Fourteen patients were previously affected by classical CD (5.6% of the overall patients with classical CD), and four were affected by subclinical CD (1.5% of the overall patients with subclinical CD). None of the patients affected by silent CD developed complications. There was no statistical difference between the mean age of the two groups developing complications (P = n.s.). Complications appeared after a mean time under GFD of 6.5 years in classical CD, and after a mean time of 3.5 years in subclinical CD (P = n.s.). Finally, 6/14 (42.8%) patients with classical CD were not fully compliant to GFD, while 2/4 (50%) of subclinical CD patients were not fully compliant to GFD (P = n.s.). Less than 5% of CD patients may develop complications under GFD. Complications seem to affect more classical CD than subclinical CD, and seem to be irrespective of optimal GFD adherence.

Celiac disease in intrauterine growth restriction

Celiac disease (CD) has been defined as a state of permanent intolerance to gluten which can be treated by a gluten-free diet and food supplements. Atypical celiac disease with only extraintestinal symptoms may be more frequent than the classical celiac disease. It has been shown that women with celiac disease experience a wide range of reproductive disorders including recurrent spontaneous miscarriage delayed menarche early menopause amenorrhoea and vaginal discharge and also intrauterine growth restriction (IUGR). The present study first of its kind in India aims to assess the frequency of latent celiac disease by means of serology in pregnant females with IUGR. The sample size of the present case controlled study was based on the reported incidence of positive serology for celiac disease in women having IUGR of around 15%. With power of test being 80% and at a chance level of 5% the estimated sample size was 45 females in each group. IgA antitissue transglutaminase antibodies are now recommended as the first-line serological test for celiac disease. The institutional ethical committee approved this study. (authors)

Small-bowel mucosal transglutaminase 2-specific IgA deposits in coeliac disease without villous atrophy: A prospective and randomized clinical study

ObjectiveIn coeliac disease, autoantibodies directed against transglutaminase 2 are produced in small-bowel mucosa, and they have been found to be deposited extracellularly. The aim of this study was to investigate whether such mucosal IgA deposits are important in the diagnostic work-up of early-stage coeliac disease without small-bowel mucosal villous atrophy.Material and methodsForty-one adults suspected of coeliac disease owing to increased density of mucosal γδ+ intraepithelial lymphocytes but normal villous morphology were randomized to gluten challenge or a gluten-free diet for 6 months. Clinically and histologically verified gluten dependency was compared with existence of small-bowel mucosal transglutaminase 2-specific extracellular IgA deposits and (coeliac disease-type) HLA DQ2 and DQ8; 34 non-coeliac subjects and 18 patients with classical coeliac disease served as controls.ResultsOf the 41 patients, 5 in the challenge group and 6 in the gluten-free diet group were clinically gluten sensitive; all 11 had HLA DQ2 or DQ8. Ten of these 11 patients showed transglutaminase 2-targeted mucosal IgA deposits, which were dependent on gluten consumption. Minimal IgA deposits were seen in only 3 out of 30 patients with suspected coeliac disease without any clinically detected gluten dependency. The deposits were found in all classical coeliac patients and in none of the non-coeliac control subjects.ConclusionsClinically pertinent coeliac disease exists despite normal small-bowel mucosal villous architecture. Mucosal transglutaminase 2-specific IgA deposits can be utilized in detecting such patients with genetic gluten intolerance.

Neurologic Complications of Celiac Disease

Source: Zelnik N, Pacht A, Obeid R, et al. Range of neurologic disorders in patients with celiac disease. Pediatrics. 2004;113:1672–1676.Investigators at the Carmel Medical Center in Haifa, Israel, sought to study the neurologic complications of celiac disease (CD) among a cohort of patients evaluated between 1977 and 2001. Patients with celiac disease [n=111] and controls [n=211] matched for age and gender were questioned regarding neurologic disorders, had their charts reviewed, and received neurologic evaluations, including brain imaging or electroencephalography, if indicated. Prior to 1988, diagnosis of CD was based on 3 consecutive intestinal biopsies. After 1988, the diagnostic approach was simplified and was based on immunoglobulin A antiendomysial antibodies and 1 intestinal biopsy. The mean age of patients and controls was 20.1 ± 9 years, and the male to female ratio was 2:3. The CD was classical infantile (diagnosed at 1.8 years) in 58 (52.3%) patients and later in onset (diagnosed at 14.8 years) in 53 (47.7%) patients. Neurologic disorders were found in 57/111 (51.4%) of patients with CD, whereas only 42/211 (19.9%) control subjects had abnormal neurologic findings. Patients with late-onset CD had more neurologic complications than the classical CD group (54.7% versus 48.3%), but the difference was not significant. Neurologic abnormalities and their frequency compared to controls included: hypotonia, 21.6% versus 3.8% (P<.01); developmental delay, 15.5% versus 3.3% (P<.01); seizures, 7.2% versus 0.8% (P<.09); learning disabilities and ADHD, 20.7% versus 10.5% (P<.01); headache, 27.9% versus 8.1% (P<.01); ataxia, 5.4% versus 0% (P<.01); and tics, 0.9% versus 2.4% (P=.67). Seizure disorders were more frequent with CD but not significantly, and tic disorders showed no increased prevalence. The gluten-free diet only benefited those CD patients with infantile hypotonia and migraine headache.The range of neurologic disorders associated with CD is wider than previously reported and includes chronic migraine headache, developmental delay, hypotonia in infants, learning disabilities, ADHD,1,2 and seizures. Apart from cases of epilepsy with occipital calcifications, recurrent seizures were not significantly correlated with CD.In occipital lobe seizures related to CD, the CD may be clinically asymptomatic.3 The incidence of silent CD in children with idiopathic localization epilepsies and the indications for routine CD screening were established in a study of 72 patients (mean age, 12.6 years) observed over a 5-year period.4 Two (8%) of 25 patients with childhood partial epilepsy with occipital paroxysms (CPEO) had positive IgA-antiendomysium antibodies, and jejunal biopsies showed villous atrophy and crypt hyperplasia, confirming the diagnosis of CD. Brain CT showed occipital calcifications in one. Seizures were controlled by treatment with a gluten-free diet, and no brain calcifications developed in the patient with a normal CT after a 3-year follow-up on a gluten-free diet.Forty-seven patients with childhood partial epilepsy with centrotemporal spikes (CPEC) had negative antibody tests for CD.4 CD screening is recommended in children with CPEO but not in those with CPEC and extraoccipital spikes. Early diagnosis and dietary intervention may reverse the tendency to seizures and brain calcifications. The gluten-free diet was also successful in the relief of migraine headaches. Wheat cereal is a known migraine trigger in some children5 and positive reactors should be screened for CD.The underlying pathophysiology linking gluten to neurologic disorders is not well characterized in this study, which refers only to its non-specific immunologic and inflammatory effects. Nonetheless, the association between gluten and brain disorders appears to be very strong, and some patients’ neurologic symptoms remit when gluten is removed from their diet. Thus, to separate the wheat of celiac disease-associated neurologic disorders from the chaff of the truly idiopathic, we must consider celiac disease as a possible etiology for a variety of neurologic presentations.

Villous tip intraepithelial lymphocytes as markers of early‐stage coeliac disease

Background: An investigation was conducted to determine whether the density of small‐intestinal villous tip intraepithelial lymphocytes would be of value in clinical practice in uncovering early‐stage coeliac disease. Methods: Villous tip, CD3+ and γδ+ intraepithelial lymphocytes were counted in patients with definite early‐stage coeliac disease without villous atrophy, in classic coeliac disease with manifest mucosal lesion and in non‐coeliac controls with normal mucosal structure. Villous tip analysis was made of haematoxylin‐eosin specimens and CD3+ and γδ+ of immunohistochemical stainings from frozen samples. Results: The villous tip intraepithelial lymphocyte count was statistically significantly higher in patients with early‐stage coeliac disease than in non‐coeliac controls. The sensitivity of this method to detect untreated coeliac disease with normal villous architecture was 0.84; the specificity was 0.88. This method proved superior to CD3+ analysis and was at least as good as γδ+ analysis in detecting early‐stage coeliac disease. In detecting classic coeliac disease, villous tip analysis also reached a higher sensitivity than CD3+ and γδ+ cells. Conclusions: Villous tip analysis seems to distinguish early coeliac from non‐specific changes, thus providing a valuable tool in routine practice, especially when borderline findings are involved. Its value appears to be similar to counting of γδ+ cells, which, however, requires frozen biopsy samples.

Screening for celiac disease in children with type 1 diabetes: two views of the controversy.

Celiac sprue is a chronic intestinal disorder caused by hypersensitivity to prolamins, the glutamine- and proline-rich gluten proteins contained in wheat, rye, and barley. Genetically predisposed subjects who ingest cereal proteins develop an inflammatory enteropathy characterized by proliferation of intraepithelial lymphocytes, crypt hyperplasia, and partial or complete atrophy of small intestinal villi. The inflammatory response is induced by cross-linking and transamidation of gluten peptides by tissue transglutaminase, an enzyme localized to the connective tissue (lamina propria or endomysium) underlying the epithelial cells of the small intestine. Posttranslational modification of gluten enhances its uptake by dendritic cells and its binding to HLA-DQ2 and DQ-8, which induce T-cell activation and cytokine release (1,2). The resulting inflammation is accompanied by development of circulating antibodies to transglutaminase and to the endomysium. Inflammatory denudation of the villous surface gives rise to malabsorption of foodstuffs, folate, fat-soluble vitamins, and iron. Young children with classical symptomatic celiac disease may present with diarrhea and growth failure, muscle wasting, hypotonia, pallor, edema, anemia, and in some cases, rickets. Older children and adults with classical celiac disease may have episodic diarrhea, steatorrhea, weight loss, and osteoporosis, and the risk of gastrointestinal malignancy is increased (3–7). However, many children and adults with celiac disease have nonclassical forms of the illness. So-called silent celiac disease refers to partial or complete villous atrophy in a seropositive patient who has no gastrointestinal or extra-intestinal complications. Subclinical celiac disease refers to villous atrophy in a seropositive patient who has extra-intestinal complications but few or no gastrointestinal complaints. Extra-intestinal maladies associated with celiac disease may include anovulation, infertility and miscarriage, neurologic disorders and epilepsy, and hepatocellular dysfunction. Studies in Western Europe, North America, and Australia indicate that the prevalence of celiac disease among children and adults with type 1 diabetes (mean 4.1%, …

Genetic dissection between coeliac disease and dermatitis herpetiformis in sib pairs.

Gluten sensitive enteropathy has various manifestations, of which the two major forms are classical coeliac disease (cCD) and dermatitis herpetiformis (DH). In cCD predominantly the small intestine is affected, whereas in DH also the skin is affected showing typical rash and IgA deposits. The symptoms in both forms are dependent on gluten intake. The factors diversifying these two clinical outcomes are unknown. In the present report we evaluated the role of the major genetic susceptibility locus, HLA DQ, in 25 families, in which both forms of the disease, cCD and DH, occurred in siblings. By using the family-based approach it can be assumed that within each family variation in environmental factors is substantially lower than in the standard case-control setting, and also the problems related to population stratification can be avoided. Results from the Finnish family material with 25 discordant and 85 concordant sib pairs, and from additional case-control material comprising 71 unrelated Hungarian DH and 68 cCD patients, together indicated that the HLA DQ locus did not differ between the two major outcomes of gluten sensitive enteropathy. The non-HLA DR;DQ factors are critical for the different clinical manifestations of gluten sensitivity.

Hypertransaminasemia in pediatric celiac disease patients and its prevalence as a diagnostic clue.

The aims of this study were to evaluate the following: 1) the prevalence of hypertransaminasemia (HT) in a pediatric celiac disease (CD) and its relation with clinical parameters; 2) the frequency of HT as the only manifestation of pediatric CD; and 3) the evolution of HT after a gluten free diet. A total of 114 consecutive pediatric CD patients were studied (60% with classical and 40% with atypical forms). Antiendomisyum antibodies and anti-tissue transglutaminase antibodies were determined in patients with a clinical suspicion of CD (including unexplained chronic HT), in patients at risk, and in patients with preoperative increased ALT activity for minor surgery. CD was confirmed by duodenal biopsy. At baseline, the relationship between clinical factors and aminotransferase status was univariately and multivariately assessed. After starting a gluten free diet, patients were followed up, until serological markers cleared and serum aminotransferase normalized. HT occurred in 32% of patients (37 of 114) at diagnosis. HT was the only manifestation of CD in five patients (4.3%). Patients with HT were younger (2.9 +/- 0.4 yr) than patients with normal aminotransferases (5.1 +/- 0.5 yr) (p = 0.007). A higher percentage of patients with classical CD tend to have abnormal aminotransferases (73%; 95% CI = 65-81%) than do patients with atypical CD (27%; 95% CI = 19-35%) (p = 0.068). Logistic regression analysis showed that only younger age was significantly associated with HT (p = 0.039; OR = 0.8; 95% CI = 0.71-0.99). Aminotransferases normalized with a gluten free diet in all 35 patients who were followed-up, either before (n = 18) or at the same time (n = 17) as serological markers cleared. HT is a frequent finding in pediatric CD patients and, in a substantial proportion, may be the only manifestation of CD. Thus, serological markers of CD should be introduced in the first step of the diagnostic workup of liver diseases in pediatric patients.

Hypertransaminasemia in pediatric celiac disease patients and its prevalence as a diagnostic clue

OBJECTIVES: The aims of this study were to evaluate the following: 1) the prevalence of hypertransaminasemia (HT) in a pediatric celiac disease (CD) and its relation with clinical parameters; 2) the frequency of HT as the only manifestation of pediatric CD; and 3) the evolution of HT after a gluten free diet. METHODS: A total of 114 consecutive pediatric CD patients were studied (60% with classical and 40% with atypical forms). Antiendomisyum antibodies and anti-tissue transglutaminase antibodies were determined in patients with a clinical suspicion of CD (including unexplained chronic HT), in patients at risk, and in patients with preoperative increased ALT activity for minor surgery. CD was confirmed by duodenal biopsy. At baseline, the relationship between clinical factors and aminotransferase status was univariately and multivariately assessed. After starting a gluten free diet, patients were followed up, until serological markers cleared and serum aminotransferase normalized. RESULTS: HT occurred in 32% of patients (37 of 114) at diagnosis. HT was the only manifestation of CD in five patients (4.3%). Patients with HT were younger (2.9 ± 0.4 yr) than patients with normal aminotransferases (5.1 ± 0.5 yr) ( p = 0.007). A higher percentage of patients with classical CD tend to have abnormal aminotransferases (73%; 95% CI = 65–81%) than do patients with atypical CD (27%; 95% CI = 19–35%) ( p = 0.068). Logistic regression analysis showed that only younger age was significantly associated with HT ( p = 0.039; OR = 0.8; 95% CI = 0.71–0.99). Aminotransferases normalized with a gluten free diet in all 35 patients who were followed-up, either before (n = 18) or at the same time (n = 17) as serological markers cleared. CONCLUSIONS: HT is a frequent finding in pediatric CD patients and, in a substantial proportion, may be the only manifestation of CD. Thus, serological markers of CD should be introduced in the first step of the diagnostic workup of liver diseases in pediatric patients.

Prevalence and clinical picture of celiac disease in Turner syndrome.

A multicenter study of Turner syndrome (TS) patients was carried out to estimate the prevalence of celiac disease (CD) and to detect clinical characteristics and laboratory data of affected patients. Three hundred eighty-nine girls with TS were screened by IgA antigliadin antibodies and/or antiendomysial antibodies. Intestinal biopsy was offered to positive cases. CD was diagnosed in 25 patients. In celiac subjects, anemia, anorexia, and delayed growth (with respect to Italian TS curves) were frequently present; whereas distended abdomen, chronic diarrhea, constipation, and vomiting occurred more rarely. In addition, low serum iron levels, hemoglobinemia, and high values of aminotransferases were observed. Ten patients showed classic CD, 8 showed atypical symptoms, and 7 showed a silent CD. In 11 symptomatic patients, the diagnosis of CD was made at the onset of symptoms, whereas 7 of them showed a median delay of 79 months in diagnosis. Other autoimmune disorders were observed in 40% of the patients. Our study confirms the high prevalence (6.4%) of CD in a large series of TS patients. Moreover, the subclinical picture in 60% of the cases, the diagnostic delay, and the incidence of other autoimmune disorders suggest that routine screening of CD in TS is indicated.

Genetic dissection between coeliac disease and dermatitis herpetiformis in sib pairs

Gluten sensitive enteropathy has various manifestations, of which the two major forms are classical coeliac disease (cCD) and dermatitis herpetiformis (DH). In cCD predominantly the small intestine is affected, whereas in DH also the skin is affected showing typical rash and IgA deposits. The symptoms in both forms are dependent on gluten intake. The factors diversifying these two clinical outcomes are unknown. In the present report we evaluated the role of the major genetic susceptibility locus, HLA DQ, in 25 families, in which both forms of the disease, cCD and DH, occurred in siblings. By using the family‐based approach it can be assumed that within each family variation in environmental factors is substantially lower than in the standard case‐control setting, and also the problems related to population stratification can be avoided. Results from the Finnish family material with 25 discordant and 85 concordant sib pairs, and from additional case‐control material comprising 71 unrelated Hungarian DH and 68 cCD patients, together indicated that the HLA DQ locus did not differ between the two major outcomes of gluten sensitive enteropathy. The non‐HLA DR;DQ factors are critical for the different clinical manifestations of gluten sensitivity.

Gluten sensitivity in sporadic and hereditary cerebellar ataxia

Gluten sensitivity, with or without classical celiac disease symptoms and intestinal pathology, has been suggested as a potentially treatable cause of sporadic cerebellar ataxia. Here, we investigated the prevalence of abnormally high serum immunoglobulin A (IgA) and IgG anti-gliadin antibody titers and typical human lymphocyte antigen (HLA) genotypes in 50 patients presenting with cerebellar ataxia who were tested for molecularly characterized hereditary ataxias. A high prevalence of gluten sensitivity was found in patients with sporadic (7/26; 27%) and autosomal dominant (9/24; 37%) ataxias, including patients with known ataxia genotypes indicating a hitherto unrecognized association between hereditary ataxias and gluten sensitivity. Further studies are needed to determine whether gluten sensitivity contributes to cerebellar degeneration in patients with hereditary cerebellar ataxia. Patients with hereditary ataxia (including asymptomatic patients with known ataxia genotype) should be considered for screening for gluten sensitivity and gluten-free diet trials.

Gluten sensitivity in sporadic and hereditary cerebellar ataxia

Gluten sensitivity, with or without classical celiac disease symptoms and intestinal pathology, has been suggested as a potentially treatable cause of sporadic cerebellar ataxia. Here, we investigated the prevalence of abnormally high serum immunoglobulin A (IgA) and IgG anti-gliadin antibody titers and typical human lymphocyte antigen (HLA) genotypes in 50 patients presenting with cerebellar ataxia who were tested for molecularly characterized hereditary ataxias. A high prevalence of gluten sensitivity was found in patients with sporadic (7/26; 27%) and autosomal dominant (9/24; 37%) ataxias, including patients with known ataxia genotypes indicating a hitherto unrecognized association between hereditary ataxias and gluten sensitivity. Further studies are needed to determine whether gluten sensitivity contributes to cerebellar degeneration in patients with hereditary cerebellar ataxia. Patients with hereditary ataxia (including asymptomatic patients with known ataxia genotype) should be considered for screening for gluten sensitivity and gluten-free diet trials. Ann Neurol 2001;49:540–543

Celiac disease in Turkish children: presentation of 104 cases.

Celiac disease is characterized by life-long gluten intolerance. Clinical features of patients with celiac disease are variable. In the present study, clinical, laboratory and histologic features of 104 patients with celiac disease were evaluated. 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. The mean (+/- SD) patient age was 5.9 +/- 4.1 years (range 10 months-16 years) and the most common symptom was diarrhea (81.7%) followed by abdominal distention, weight loss, anorexia and failure to thrive. Abdominal distention (60.6%), short stature (45.2%) and iron-deficiency anemia were the most common findings. High serum alanine aminotransferase levels were found in 38.3% of patients and these levels became normal after adoption of a gluten-free diet in all but two patients with cirrhosis. Immunoglobulin A, IgG antigliadin antibodies and IgA anti-endomysium antibodies were found in 76, 94 and 90% of patients, respectively. Biopsy of the small intestine revealed that 95, two and seven patients had type 3, type 2, and type 1 lesions, respectively, according to the Marsh classification. There was no statistically significant difference between patients and control groups with regard to antinuclear antibody, antismooth muscle antibody, anti-DNA and anticardiolipin antibodies (IgG and IgM). Although classical celiac disease was seen in most patients in the present study, clinical variability of the condition should be kept in mind. In particular, patients with uncommon findings, such as short stature, cryptogenic liver disease and iron-deficiency anemia, should also be screened for celiac disease.

Celiac disease and idiopathic cerebellar ataxia

Accurate diagnosis of celiac disease (CD) is challenging because gastrointestinal symptoms may be entirely absent or may be overshadowed by extraintestinal complaints.1 Neurologic complications (especially cerebellar ataxia) occur in about 10% of patients, with the classic CD featuring weight loss and diarrhea. However, two recent studies2,3 have shown a high frequency of serologic evidence of gluten sensitivity with or without histologic evidence of CD in patients with idiopathic cerebellar ataxia (ICA), and in the absence of gastrointestinal symptoms or malabsorption signs. ICA refers to a group of sporadically occurring cerebellar degenerations of unknown etiology that are clinically characterized by …

Intestinal lymphangiectasia associated with deep vein thrombosis. First results in treatment with octreotide

Background & Aim: Intolerance to dietary gluten in celiac disease has traditionally been considered to persist lifelong, although the possibility of transient intolerance has been proposed. Whether patients can 'grow out' of true celiac disease and the frequency with which this may occur, is unclear. We performed a detailed review of clinical, serologic and histologic evidence for gluten intolerance in adult subjects over two decades after they were diagnosed as celiac in childhood. Methods: 103 patients diagnosed with celiac disease in childhood in a pediatric unit with special interest in the condition were contacted and reviewed 23-39 years after their original diagnosis. Original diagnostic criteria used at the time were histologic evidence of celiac disease above the age of 24 months, a clinical response to a gluten-free diet, and proven clinical and histologic response to gluten exclusion. After reassessment in adulthood, we offered endoscopic distal duodenal re-biopsy to patients who were not adhering to a gluten-free diet and in whom endomysial antibodies were negative. Results: Six patients have been identified who initially fulfilled traditional criteria for celiac disease but now have no evidence for gluten sensitivity on reassessment in adulthood, while on a full gluten-containing diet. Each patient presented with malabsorption within the first 2 years of life and had a subsequent jejunal biopsy that showed moderate (l/6) to severe villous atrophy (5/6). Evidence for malabsorption resolved on a gluten-free diet, and each had a subsequent small bowel biopsy 1-11 years later which, although improved, was still abnormal (partial villous atrophy in 3 cases and increased intraepithelial lymphocytes in the other 3 cases). In adulthood, while taking a full gluten-containing diet, none of the patients now have evidence of malabsorption, serum endomysial antibodies are negative, and distal duodenal biopsies have been normal in all. Conclusion: The observations provide evidence in favor of the occurrence of true transient gluten intolerance in some patients with apparent classical childhood celiac disease. That each patient had two abnormal biopsies at different intervals during childhood (albeit with improvement on gluten restriction) supports the validity of the original diagnosis and suggests that the initial abnormality was not due to one of the mimics of celiac disease in childhood. The results also support the view that the requirement for rigid adherence to a gluten-free diet may diminish and resolve in adulthood in a proportion of patients.

Regional Differences in Coeliac Disease Prevalence in Scandinavia?

Background: According to investigations from the central region of Sweden (Linköping), Norway, and Finland based on antibody screening, the prevalence of coeliac disease (CD) is around 1:300 (0.33%). In Denmark surveys in paediatric departments have shown a prevalence of only 1:10,000. The aim of the present study was to study the prevalence of CD in southern Sweden. Methods: From October 1996 to February 1997, 1970 healthy blood donors were screened for CD in a serial procedure: first IgA and IgG gliadin antibodies (GA) and then endomysial antibodies in those positive for GA. Results: One patient had previously known CD. Two patients had gastrointestinal symptoms and an increased number of intraepithelial lymphocytes, with improvement on a gluten-free diet. Three of 185 GA-positive blood donors had endomysial antibodies and biopsy-verified CD. Thus, 4 of 1970 blood donors had classic CD, resulting in a prevalence of 1:492 (0.20%)—that is, rather similar to that found in Linköping, Sweden, and in Finland and Norway. If the two persons with gluten-sensitive diarrhoea were also included, the prevalence was 6:1970 = 1:328, or 0.30%. Conclusions: The prevalence of classic CD (1:492) in southern Sweden is comparable to that found in the rest of Scandinavia, except for Denmark.