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PubMed1996

Celiac disease is a lifelong disorder.

Celiac disease has always been considered a permanent condition. A relapse, defined on the basis of mucosal changes, occurring within 2 years of reintroducing gluten to a patient's diet (challenge) has been taken as confirmation of the permanence of the disease. Some observers have questioned whether the disease is permanent, since long periods of unexplained clinical remission occur, mainly among adolescents. However, the presence or absence of symptoms has no correlation with the histologic activity of the disease or with the results of serologic tests. With very few exceptions, patients in whom celiac disease is diagnosed during their childhood eventually have a relapse. However, in some cases, many years may elapse before a relapse; therefore, the 2-year limitation is no longer considered valid. On the other hand, there have been anecdotal observations that some patients eating a normal diet containing gluten appear to have experienced a "natural recovery." This recovery is partial and probably temporary, since there is evidence that celiac disease can be present in a latent form. Long-term randomized studies, in which morphometric and ultrastructural measurements are taken, that show villous integrity, the absence of abnormal inflammation and a lack of long-term complications of a diet containing gluten are needed before the current "zero-gluten" approach to celiac disease is altered. The individual variation in the extent and time course of celiac disease does not contradict the evidence that the disease persists throughout life, actively, silently or latently. Currently, there is no justification for recommending long-term consumption of gluten for either children or adults with celiac disease.

Adolescent↗

PubMed2005

High prevalence of celiac disease among patients affected by Crohn's disease.

BACKGROUND: Recent literature has shown a correlation between Crohn's disease (CD) and celiac disease, but a prospective study has not been performed. Our aim was to evaluate the prevalence of celiac disease in a consecutive series of patients affected by CD, in whom the disease was diagnosed for the first time. METHODS: From January to December 2004, we diagnosed 27 patients affected by CD (13 men and 14 women; mean age, 32.3 yrs; range, 16-69 yrs). In all patients, we performed antigliadin, antiendomysium, and antitransglutaminase antibody tests, and the sorbitol H2 breath test evaluation. In case of antibodies and/or sorbitol positivity, esophagogastroduodenoscopy was performed for a small bowel biopsy. RESULTS: Antigliadin, antiendomysium, and antitransglutaminase antibody tests were positive in 8/27 (29.63%), 4/27 (14.81%), and 5/27 (18.52%) patients, respectively, whereas the sorbitol H2 breath test was positive in 11/27 (40.74%) patients: all of them underwent esophagogastroduodenoscopy. Nine of 11 patients showed signs of duodenal endoscopic damage, and 5/9 (55.55%) showed histologic features of celiac disease (18.52% of overall CD population studied): 2 showed Marsh IIIc lesions (1 patient affected by ileal CD and 1 affected by ileo-colonic CD), 2 showed Marsh IIIb lesions (all of them affected by ileo-colonic CD), 1 showed a Marsh IIIa lesion (1 patient affected by colonic CD). CONCLUSIONS: Prevalence of celiac disease seems to be high among patients affected by CD, and this finding should be kept in mind at the time of the first diagnosis of CD; a gluten-free diet should be promptly started.

Adolescent↗

PubMedDate not supplied

[The global village of celiac disease].

Recent data suggest that celiac disease, or gluten-sensitive enteropathy, is a common disorder not only in populations of European ancestry, but also in developing areas, such as North Africa, Middle East and India. The world distribution of celiac disease apparently relates to the consumption of gluten-containing cereals. In the Arab people of Saharawi, the prevalence of celiac disease in children is so high (more than 5%) that this condition represents a primary health problem. In developing countries the clinical picture of celiac disease is often typical, characterized by chronic diarrhea, malnutrition, stunting and increased mortality, especially in younger children. The high prevalence of celiac disease in areas showing a poor sanitary condition could be explained by a protective role of the celiac enteropathy (against intestinal infections) in the context of a low gluten consumption. The problem of celiac disease in developing countries should by approached by a multifaceted strategy, based on (1) increasing disease awareness and diagnostic facilities and (2) a "flexible" dietary intervention that takes into account the nutritional habits and local food availability.

Adult↗

PubMed2003

[Antitransglutaminase antibodies determination for the diagnosis of celiac disease].

BACKGROUND: The diagnosis of celiac disease is based in clinical features, serology and intestinal biopsy. There are recent reports that antiglutaminase antibodies have a good correlation with anti endomisial antibodies. AIM: To assess the sensitivity and specificity of antitransglutaminase antibodies in the diagnosis of celiac disease and their correlation with antiendomisial antibodies. MATERIAL AND METHODS: Forty nine patients with celiac disease (mean age 30 years, 12 male) were studied. Thirty were symptomatic and 19, asymptomatic. As controls, 34 subjects (mean age 27 years, seven male), with normal duodenal biopsies, were studied. Sera was processed for the determination of antigliadin IgA by ELISA, antiendomisium IgA by indirect immunofluorescence, and antitransglutaminase IgA by ELISA. RESULTS: Antigliadin antibodies had a sensitivity of 73%, a specificity of 96%, a positive predictive value of 93% and a negative predictive value of 82% for the diagnosis of celiac disease. Antiendomisium and antitransglutaminase antibodies had a specificity and positive predictive value of 100%, sensitivities of 89 and 92% respectively and negative predictive values of 92 and 94% respectively. No significant differences in the diagnostic yield of antiendomisium and antitransglutaminase antibodies, were observed. CONCLUSIONS: In this group of patients, antitransglutaminase antibodies had a high concordance with antiendomisium antibodies, for the diagnosis of celiac disease. Considering that the determination of antitransglutaminase antibodies is of lower cost and less complicated than antiendomisium antibodies, it is a useful tool for the diagnosis and follow up of patients with celiac disease.

Adolescent↗

PubMedDate not supplied

Immunopathogenesis of celiac disease.

The immunopathogenesis of celiac disease requires interactions between genetic, environmental and immunologic factors. Genes within the class II region of the major histocompatibility complex (HLA-D region) represent a major component contributing to disease susceptibility. Structural studies of genes within the HLA-D region have shown that the class II HLA haplotype associated with celiac disease is extended, and includes not only the HLA-DR and DQ subregions, but also the HLA-DP subregion. The celiac disease-associated haplotype is marked in the HLA-DP subregion by a polymorphic 4 kilobase Rsa I genomic fragment derived from a DP beta chain. Other studies suggest that, in addition to dietary gliadins, a viral protein may play a role in the pathogenesis of celiac disease, perhaps by virtue of immunologic cross reactivity between antigenic determinant shared by the viral protein and alpha gliadins.

Antibody Formation↗

PubMed2006

Celiac disease in African-Americans.

Celiac disease is generally under diagnosed in the United States and it is unclear whether the disease is encountered in ethnic minorities. Our purpose is to describe a case series of African-American patients with celiac disease. Nine (1.3%) African-American patients with celiac disease were identified from a prospectively generated database of 700 patients with biopsy proven celiac disease and seen between 1981 and 2004. Females predominated, with seven, compared to two males. Diarrhea was the presentation in only two patients, while three presented with iron deficiency anemia. One third had at least one autoimmune disease. Compliance with a gluten-free diet, the only medical therapy of this disease, was poor. Only four patients adhered strictly to the diet. Celiac disease occurs in African-Americans and may well be underdiagnosed. Special attention needs to be given to methods that encourage adherence to the diet in minority groups.

Adult↗

PubMed2004

Effect of a gluten-free diet on gastrointestinal symptoms in celiac disease.

BACKGROUND: Atypical presentations of celiac disease appear to be at least as common as is the classic presentation of steatorrhea, diarrhea, and weight loss. OBJECTIVE: We examined the effect of a gluten-free diet on gastrointestinal symptoms in a cohort of US patients with celiac disease. DESIGN: A follow-up survey was conducted in 215 patients who were evaluated at the University of Iowa from 1990 through 1997 as having biopsy-confirmed celiac disease. The systematic survey asked detailed questions regarding gastrointestinal symptoms before and after the institution of a gluten-free diet in the patients, all of whom had been given the same dietary advice. RESULTS: The group consisted of 160 female and 55 male patients. Although diarrhea was the most frequent symptom in untreated celiac disease, steatorrhea occurred in only one-fifth of patients. Other complaints were common, and most responded to gluten exclusion. The benefit of gluten exclusion was equally apparent in men and women. Diarrhea responded in most patients, usually within days, and the mean time to resolution was 4 wk. Many patients had alternating diarrhea and constipation, both of which were responsive to the gluten-free diet. Most patients had abdominal pain and bloating, which resolved with the diet. CONCLUSIONS: Celiac disease causes a wide range of gastrointestinal symptoms. Clinicians must have a high level of suspicion to detect the atypical forms of celiac disease. With a gluten-free diet, patients have substantial and rapid improvement of symptoms, including symptoms other than the typical ones of diarrhea, steatorrhea, and weight loss.

Body Mass Index↗

PubMed1997

Is celiac disease associated with Alzheimer's disease?

An increased prevalence of celiac disease has been reported in neurological disorders of unknown etiology. A large proportion of Alzheimer's cases is still of unexplained etiology. Thirty-three Alzheimer's patients and 24 elderly controls were screened for celiac disease. IgA and IgG antigliadin antibodies were assayed in serum samples with enzyme-linked immunoassay. Confirmation of celiac disease in positive subjects was made by assaying IgA anti-endomysium antibodies by indirect immunofluorescence. Two Alzheimer's patients and 2 controls were positive for antigliadin antibodies (6 versus 8%; NS). None was positive for anti-endomysium antibodies. We conclude that the prevalence of celiac disease in Alzheimer's disease is not higher than in cognitively unimpaired elders, suggesting that the immune changes in celiac disease are unlikely to play a role in Alzheimer's disease.

Aged↗

PubMed1998

[Simultaneous presentation of autoimmune thyroiditis and celiac disease in an adult].

Celiac disease may be associated with other underlying autoimmune diseases. Among these, thyroid disease has been described in around 10% of the cases with hypothyroidism being the most frequently reported. Clinical suspicion of thyroid involvement in patients with celiac disease is difficult since the symptomatology is scarce or is masked by the picture of malabsorption. Nonetheless, its detection is important since it is not solved by gluten free diet and its correction requires specific treatment. Thyroid function studies, in addition to determination of antithyroglobulin and antimicrosomal antibodies, should be considered in celiac patients refractory to conventional dietetic treatment. We herein present the case of a 65-year-old woman who consulted for a malabsorption syndrome in whom celiac disease of the adult was simultaneously presented with hyperthyroidism secondary to autoimmune thyroiditis.

Aged↗

PubMed1993

Spectrum of expression of intestinal cellular immunity: proposal for a change in diagnostic criteria of celiac disease.

The clinical heterogeneity of celiac disease is well recognized, with great variability in malabsorption and in gastrointestinal symptoms of patients with active celiac disease, and the fairly common occurrence of silent celiac disease (ie, an apparently healthy individual with a flat small bowel mucosa). Research in experimental animals has shown that expression of cell-mediated immunity in the gut mucosa occurs in a spectrum of pathologies ranging from minimal enteropathy with a high count of intra-epithelial lymphocytes to the celiac-like lesion with short villi and long crypts. A similar range of pathology is seen in celiac patients in some circumstances, with low grade enteropathy occurring in the early stages of gluten challenge, in patients taking a low gluten diet, and also in some patients with dermatitis herpetiformis. In so-called latent celiac disease, sophisticated immunologic studies may reveal a high intra-epithelial lymphocyte count, an increased gamma delta intra-epithelial lymphocyte count, and a celiac-like intestinal antibody abnormality with overexpression of mucosal IgM responses. If further work confirms that one or more of these features may be the only manifestation of gluten-sensitive disease in some newly presenting patients, the current definition of celiac disease (a flat mucosa, gluten-sensitive) will need to be revised.

Biopsy↗

PubMed1996

Is celiac disease a lifelong disorder?

That celiac disease is a lifelong disorder was suggested by clinical case records and was considered to have been demonstrated through the widespread use of intestinal biopsies by the end of the 1950s. It was clear that the mucosal lesions observed in children and adults were identical and responded similarly to gluten withdrawal. In fact, in 1970 the European Society for Paediatric Gastroenterology and Nutrition instituted the practice of a challenge after diagnosis. A relapse of clinical symptoms and of the intestinal lesions after gluten was reintroduced into the diet demonstrated the "permanent" nature of sensitivity to gluten in children with celiac disease. Twenty-five years later, the permanence of the sensitivity of the intestinal mucosa to gluten is again a matter of debate. Several lines of evidence, gathered during recent years, show that celiac disease is not always a lifelong condition. First, the long-term follow-up of children with proven celiac disease shows that 10% to 20% of them become "tolerant" (defined on clinical, biological and histologic grounds) to gluten during adolescence. Second, it has also been shown, in individual cases, that the mucosal lesions typical of the disease may appear during adulthood. Our increasing knowledge of the long-term evolution of the disease suggests that celiac disease develops and, in some cases, fades in a predisposed group of people with intestinal sensitivity to gluten, which is probably a common condition. The factors leading to the appearance or disappearance of the disease, however, are still unknown.

Adolescent↗

PubMed1994

Celiac disease: clinical features and pathogenesis.

Celiac disease is a fascinating illness, from both a clinical and research perspective. Most clinicians consider a diagnosis of celiac disease when a young patient has classic signs and symptoms of steatorrhea and severe malabsorption. However, the typical gastrointestinal symptoms often are absent. The patient may only have subtle signs of chronic malnutrition or nonspecific gastrointestinal complaints. Celiac disease is not diagnosed commonly in the United States, at least in part because of a low clinical index of suspicion. A diagnosis of celiac disease is confirmed by a small bowel mucosa biopsy. A dramatic clinical response to a gluten-free diet verifies the diagnosis, and provides a cost-effective treatment free of significant side effects. Strict adherence to the prescribed diet usually results in a complete resolution of the symptoms and mucosal histopathologic changes. The serious, long-term complication of intestinal lymphoma also may be prevented. To the clinical investigator, celiac disease is an important model of the HLA-associated immune-mediated illnesses. A specific HLA-DQ heterodimer is found in 95% of patients, representing perhaps the strongest association of any illness with a specific class II HLA molecule. In addition, an important environmental trigger (gluten) has been identified, providing a unique opportunity to study the interaction of gene products and environmental factors in the pathogenesis of an immune-mediated disease.

Celiac Disease↗

PubMed2006

Prevalence of autoantibodies associated with thyroid and celiac disease in Ullrich-Turner syndrome in relation to adult height after growth hormone treatment.

A prospective, multicenter study of patients with Ullrich-Turner syndrome (UTS) was conducted to estimate the prevalence of autoantibodies to tissue transglutaminase (tTg), thyroid stimulating hormone receptor (TSH-R), thyroglobulin (TG) and thyroid peroxidase (TPO) in relation to adult height after long-term growth hormone (GH) treatment. Out of 347 near-adult (> 16 years) patients with UTS from 96 German centers, whose longitudinal growth was documented within the Pharmacia International Growth Study (KIGS), 188 returned for a standardized follow-up visit at a median chronological age of 18.7 (16.0-23.6) years (bone age > 15 years). Serum samples of 120 patients were obtained for central measurements of TSH, thyroxine (T4) and free T4 and autoantibodies by standard immunoassays. Information regarding thyroid disease, karyotype and anthropometric data was extracted from the KIGS database. Thirty-six percent of the patients with UTS had positive TG and/or TPO autoantibodies and 4% had positive tTg autoantibodies, whereas 2% had positive TG and/or TPO autoantibodies as well as positive tTg autoantibodies. TSH-R autoantibodies were undetectable in all patients. The detection of autoantibodies was unrelated to a specific karyotype. Median height standard deviation scores (SDS, UTS) at start of GH treatment (0.43; -1.07, 1.85) and at follow-up (1.36; -0.11, 2.57) were comparable in all patients independent of their antibody status. The total deltaheight SDS, however, was higher in patients with negative autoantibody titers (1.08; -0.03, 2.25) compared to those with positive antibody titers (0.68; -0.44, 1.82; p < 0.01). Our study confirms the high prevalence of autoantibodies in patients with UTS predisposing them to autoimmune thyroid disease and celiac disease, and indicates for the first time that autoimmune pathologies may interfere with GH therapy and thus compromise final height. Therefore, medical care for patients with UTS should routinely include screening for these autoimmune disorders in order to assure early detection and appropriate treatment.

Adolescent↗

PubMed2006

Autologous hematopoietic stem cell transplantation in refractory celiac disease with aberrant T cells.

Autologous hematopoietic stem cell transplantation (ASCT) is an increasingly accepted treatment for refractory autoimmune diseases. Refractory celiac disease with aberrant T cells (RCD type II) is unresponsive to available therapies and carries a high risk of transition into enteropathy associated T-cell lymphoma (EATL). This study reports on the feasibility, safety, and efficacy of ASCT in patients with RCD type II. Thirteen patients with RCD type II were evaluated. Seven patients (4 men, 3 women, mean age 61.5 years [range, 51-69 years]) underwent transplantation. After conditioning with fludarabine and melphalan, ASCT was performed. Patients were monitored for response, adverse effects, and hematopoietic reconstitution. All 7 patients completed the mobilization and leukapheresis procedures successfully and subsequently underwent conditioning and transplantation. Engraftment occurred in all patients. No major nonhematologic toxicity or transplantation-related mortality was observed. There was a significant reduction in the aberrant T cells in duodenal biopsies associated with improvement in clinical well-being and normalization of hematologic and biochemical markers (mean follow-up, 15.5 months; range, 7-30 months). One patient died 8 months after transplantation from progressive neuroceliac disease. These preliminary results showed that high-dose chemotherapy followed by ASCT seems feasible and safe and might result in long-term improvement of patients with RCD type II whose condition did not respond promptly to available drugs.

Aged↗

PubMed2002

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.

Antibodies, Monoclonal↗

PubMed2003

Identification of new celiac disease autoantigens using proteomic analysis.

Celiac disease is an autoimmune disorder in which gluten peptides presented by specific HLA-DQ2- and HLA-DQ8-positive antigen presenting cells elicit immune response in connective tissue of lamina propria. Immunoglobulin A (IgA) antiendomysial antibodies are specific for celiac disease and are used for screening, diagnosis and follow-up of this disease with an almost 100% sensitivity and specificity. The major target antigen of IgA antiendomysial antibodies was identified as tissue transglutaminase; nevertheless, the existence of the additional unique celiac disease-specific autoantigens is anticipated. In this study we have utilized a proteomic approach in order to search out new autoantigens recognized by serum antibodies of patients with active celiac disease. We report the detection of 11 proteins that were immunorecognized with various frequencies by sera of patients with celiac disease. Four autoantigens were identified by mass fingerprinting approach as actin, ATP synthase beta chain and two charge variants of enolase alpha. While production of IgA antibodies against actin molecules were described earlier, the existence of autoantibodies to ATP synthase beta chain and enolase alpha species in sera collected from patients with active celiac disease are described for the first time. These results are suggestive of the existence of additional celiac disease autoantigens with possible diagnostic utility.

Adult↗

PubMed1981

Acetaminophen absorption and metabolism in celiac disease and Crohn's disease.

To investigate further the conflicting results in reports of drug absorption in patients with small intestinal mucosal disease, gastric emptying and the disposition of acetaminophen were assessed simultaneously in 41 subjects (13 controls, 12 patients with Crohn's disease, and 16 with celiac disease). Acetaminophen absorption as judged by plasma concentrations and gastric emptying were slower in patients with celiac disease and Crohn's disease. Total drug absorption as indicated by urinary recovery did not differ, but plasma acetaminophen half-life was shorter and glucuronide conjugation was enhanced in the patients with Crohn's disease. Contrary to expectation, the mean rate constant for acetaminophen absorption from the small intestine was not decreased in Crohn's disease and celiac disease. The abnormally slow acetaminophen absorption in the patients with Crohn's or celiac disease could be explained by slower gastric emptying of the drug solution.

Acetaminophen↗

PubMed2006

[Atypical manifestations of celiac disease in an adult woman].

Celiac disease is intolerance to gluten that classically produces chronic diarrhea with a picture of malabsorption and a total villous atrophy. These elements regress completely in a sequential way under a prolonged gluten-free diet. We describe a case of a 35-year-old woman affected by celiac disease who presented atypically, with features including hypoproteinaemia (38g/L) with dominant hypoalbuminaemia (12g/L), weight loss, strong psychoneurotic component and amenorrhoea. These manifestations for the first time were diagnosed as irritable bowel disease and after immunology diagnostic as celiac disease. Current research on celiac disease has pointed out the biologically significant role of antigliadin antibodies IgG and IgA and antibodies to tissue transglutaminase (tTg).

Adult↗