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Complications due to late diagnosis of celiac disease with co-existing plasma cell dyscrasia in an elderly patient.

Celiac disease is a genetic disorder, presenting with malabsorption-related problems because of mucosal damage after ingestion of gluten. The only known effective treatment is a gluten-free diet. Early diagnosis and treatment are essential in preventing complications due to malabsorption. Here we report the case of an elderly patient with a fifteen-year history of diarrhea, diagnosed with celiac disease, who had developed several complications due to malabsorption such as anemia, electrolyte imbalance and osteoporosis. We believe that late diagnosis of celiac disease had played a great role in the development of complications. Moreover, celiac disease poses an increased risk for all types of malignancies. Our patient also had concurrent plasma cell dyscrasia, but did not fulfil the criteria for diagnosis of multiple myeloma.

Aged↗

Insights in the laboratory diagnosis of celiac disease.

The present report focuses on the diagnosis of celiac disease and its pathogenesis, which depends on a genetic predisposition (HLA DQ2 or DQ8 haplotypes), gluten ingestion and T cell activation, type II transglutaminase (TG2), the autoantigen recognized by the antiendomysial antibody playing a key role. IgA class antibody anti-environmental (gliadin) and endogenous (TG2) antigens are present in the sera of patients with celiac disease. The anti-TG2 antibody has the best available diagnostic accuracy, especially when measured employing second generation ELISA tests, which use the human TG2 antigen, or immunochemiluminescent assay, which is highly sensitive. A diagnosis of celiac disease must always be confirmed by the histological evaluation of multiple duodenal mucosa specimens, and serology is recommended for follow-up controls.

Antibodies↗

Levels of serologic markers of celiac disease in patients with reflux esophagitis.

AIM: To investigate the prevalence of celiac disease serologic markers (antigliadin IgA, IgG, and anti-endomysial IgA) in patients with reflux esophagitis and to detect the relationship between reflux esophagitis and celiac disease (CD). METHODS: This study was performed prospectively between January 2003 and January 2004. Sixty-eight adult reflux esophagitis patients and 40 people as control group for symptoms related with gastrointestinal system were enrolled in this study. The diagnostic work-up included an accurate medical history with gastrointestinal symptoms, routine laboratory measurements, the detection of antibodies against gliadin (IgA and IgG) and endomysium (IgA), and an upper endoscopy with postbulbar biopsy. RESULTS: IgA-AGA and IgG-AGA were positive at 8.8% and 10.3% in patients with reflux esophagitis. In control group, it was found that 10% people had positive IgA-AGA, and 7.5% people had positive IgG-AGA. There was no significant relationship between patients and control group regarding positive IgA-AGA and IgG-AGA. The patients and persons in control group had no positive IgA-EMA. On postbulbar biopsies, no finding was detected concerning celiac disease. There were no symptoms and signs for gluten enteropathy in patients and control group. CONCLUSION: This review supports that an association does not exist between celiac disease and reflux esophagitis. We think these diseases exist independently from each other.

Adult↗

Myosin IXB variant increases the risk of celiac disease and points toward a primary intestinal barrier defect.

Celiac disease is probably the best-understood immune-related disorder. The disease presents in the small intestine and results from the interplay between multiple genes and gluten, the triggering environmental factor. Although HLA class II genes explain 40% of the heritable risk, non-HLA genes accounting for most of the familial clustering have not yet been identified. Here we report significant and replicable association (P = 2.1 x 10(-6)) to a common variant located in intron 28 of the gene myosin IXB (MYO9B), which encodes an unconventional myosin molecule that has a role in actin remodeling of epithelial enterocytes. Individuals homozygous with respect to the at-risk allele have a 2.3-times higher risk of celiac disease (P = 1.55 x 10(-5)). This result is suggestive of a primary impairment of the intestinal barrier in the etiology of celiac disease, which may explain why immunogenic gluten peptides are able to pass through the epithelial barrier.

Amino Acid Sequence↗

Perceived health status in celiac disease.

INTRODUCTION: Chronic conditions modify perceived health in affected individuals. For this reason celiac disease, being a chronic condition, may impair health-related quality of life (HRQOL). OBJECTIVE: To analyze the impact of celiac disease in affected individuals. METHOD: Observational, cross-sectional, prospective study in patients with celiac disease by administering two HRQOL questionnaires: EuroQol-5D and GastroIntestinal Quality of Life (GIQLI). RESULTS: 54 stable patients on a gluten-free diet for a median 60 months, and 9 newly diagnosed individuals still on their usual diet were included. Overall GIQLI score was significantly higher, meaning a better HRQOL, in treated celiac patients versus pre-treated celiac patients (3.1 [2.7-3.5] vs. 2.4 [2.1-2.6], p < 0.01). Similarly, EuroQol s health status preference value was also significantly better in treated patients (0.87[0.8-1.0] vs. 0.7 [0.5-0.8], p < 0.01). EuroQol s visual analogic scale had also better scores, representing a better perceived health, among treated patients (80.0 [70.0-90.0] vs. 65.0 [40.0-71.0], p < 0.05). In comparison to EuroQol-5D scores among the healthy Spanish population, values obtained for celiac patients under treatment are similar to those seen in the general population. CONCLUSIONS: celiac disease impairs perceived health in affected individuals, which improves and reaches results similar to those in the general population when on a gluten-free diet.

Adult↗

Latent and potential celiac disease in epileptic Turkish children.

In this study, we measured tissue transglutaminase IgA antibody for the serologic screening of celiac disease in 70 children with epilepsy. A pathologic titer of tissue transglutaminase IgA antibody was found in eight patients (4.7%). Small intestinal biopsies were performed in all antibody-positive patients, and two of them had small bowel histology typical of celiac disease (1.17%). Six had normal histology and were considered to have potential celiac disease. The prevalence of celiac disease in the epileptic group was 1.17%. None of the serum samples of 103 healthy children comprising the control group were positive for tissue transglutaminase IgA antibody. Therefore, we suggest that epileptic children be screened for celiac disease. (J Child Neurol 2006;21:6-7).

Adolescent↗

Tissue transglutaminase--the key player in celiac disease: a review.

Gluten-sensitive enteropathy, otherwise known as celiac sprue, is characterized by an abnormal proximal small intestinal mucosa arising as a result of an inappropriate inflammatory response to ingested gluten antigens present in wheat in genetically susceptible individuals. This immune response is directed to a 33-mer peptide of the alpha gliadin component of gluten. The generation of an epitope for the recognition by CD4+ T cells requires deamination of the protein by tissue transglutaminase (tTG). Moreover, IgA anti tTG is highly sensitive and is specific serologic marker (95-99%) of celiac disease. They can be easily determined quantitatively, by ELISA of an accurate and relatively inexpensive technique. Therefore, tTG can be used as the first line diagnostic test in the work-up of celiac disease, as well as for screening purposes. Finally, tTG may contribute to future strategies in treating celiac disease either by producing nontoxic wheat or by generating oral vaccination that can prevent the disease.

Celiac Disease↗

Role of pancreatic impairment in growth recovery during gluten-free diet in childhood celiac disease.

BACKGROUND & AIMS: Clinical significance and duration of insufficient release of pancreatic enzymes in childhood celiac disease have not been clarified. The aim of this study was to evaluate the role that pancreatic impairment plays in growth recovery and the duration of this impairment. METHODS: Forty-six patients with celiac disease who had a median age of 2.5 years were enrolled. Fecal chymotrypsin level was determined at diagnosis and then every 15 days after the beginning of a gluten-free diet in all patients. RESULTS: At diagnosis, 17 of 46 patients with celiac disease had subnormal fecal chymotrypsin values. During the gluten-free diet, a progressive reduction in the percentage of patients with subnormal fecal chymotrypsin values was observed: 12 of 46 patients after 30 days and 2 of 46 patients after 60 days. Weight increase after 2 months of gluten-free diet was significantly greater in patients with normal fecal chymotrypsin values at diagnosis than in patients with subnormal values, and a positive correlation was found between fecal chymotrypsin at diagnosis and weight increase (r = 0.56). CONCLUSIONS: A small percentage of patients with celiac disease still had subnormal chymotrypsin concentrations after 60 days of gluten-free diet. Fecal chymotrypsin is a predictive index of weight recovery in the first months after diagnosis of celiac disease; it could be used to select patients for enzyme supplementation therapy.

Body Weight↗

Immunofluorescent antigluten antibody test. Titer and profile of gluten antibodies in celiac disease.

Circulating antibodies to gluten fractions have been detected in most patients with celiac disease during gluten ingestion. The various detection techniques, however, are rather complex and inadequate for routine clinical use. Recently, a new indirect immunofluorescent method, named the antigluten antibody (AGA) test, has been developed. To establish the reliability of the test we compared six groups of patients: (1) 15 patients with biopsy-proved celiac disease of whom 13 had positive test results (the other two had already been receiving a gluten-free diet for two to three weeks); (2) 13 malnourished patients without celiac disease who had damaged mucosa, of whom only two had positive test results; (3) 21 patients with celiac symptomatology but normal mucosa, of whom four had positive test results; (4) 42 patients with other intestinal tract diseases, of whom seven had positive test results; (5) 28 patients with extraintestinal diseases, of whom only two had positive test results; and (6) 26 patients with autoimmune diseases, of whom five had positive test results. All patients with celiac disease who had positive test results and who were receiving a gluten-containing diet had titers of 1:40 to 1:80 in the IgG class, while all other patients with positive AGA test results had a low titer of 1:10 to 1:40, in the IgM class mainly. We conclude that the AGA test is an effective screening tool for patients with celiac disease and may serve as a practical index of dietary gluten avoidance.

Antibodies↗

Mental disorders in adolescents with celiac disease.

A high prevalence of depressive symptoms, hypothetically related to serotonergic dysfunction, has been reported among adults with celiac disease. The authors used semistructured psychiatric interviews and symptom measurement scales to study mental disorders in 29 adolescents with celiac disease and 29 matched comparison subjects. Relative to the comparison subjects, the celiac disease patients had significantly higher lifetime prevalences of major depressive disorder (31% versus 7%) and disruptive behavior disorders (28% versus 3%). In most cases these disorders preceded the diagnosis of celiac disease and its treatment with a gluten-free diet. The prevalence of current mental disorders was similar in both groups. Celiac disease in adolescents is associated with an increased prevalence of depressive and disruptive behavioral disorders, particularly in the phase before diet treatment.

Adolescent↗

Association between celiac disease and lung disease.

An association has been suggested between celiac disease and diffuse interstitial lung disease of the hypersensitivity pneumonitis type in several reports from Europe. The present report consists of a study of 18 North American, biopsy-proved celiac patients, who were compared with an equal number of control subjects balanced for age, sex, and smoking. The celiac patients showed no evidence of interstitial lung disease as assessed by chest roentgenograms and pulmonary function tests. However, a history of asthma or chronic cough was present in a higher proportion of the celiac than control subjects. Also the celiac patients showed objective evidence of airway obstruction, as demonstrated by differences between the two groups in FEV1 (P less than 0.05) and Vmax 50% and Vmax 25% (P less than 0.01 and less than 0.05, respectively). These results confirm a recent report questioning whether there is truly a relationship between celiac disease and interstitial lung disease. Nevertheless, our findings suggest an association between celiac disease and airway obstruction.

Antigen-Antibody Complex↗

Celiac disease in two different population groups of South Tirol.

The expression of celiac disease is assumed to be influenced by both genetic and environmental factors. Our study investigated the prevalence and HLA type in two different ethnic groups: a German group and an Italian group living in South Tirol. Intermarriages are rare between these population groups. The live birth rate during 1973-1982 (10 years) was 42,739 for the German group and 14,874 for the Italian group. Fifty people with celiac disease, born during this period, were diagnosed according to the ESPGAN criteria: 45 were German and five were Italian. The incidence in the German group was 105 per 100,000, and 33 per 100,000 in the Italian group. HLA typing was performed in 40 patients, and in 50 German and 50 Italian controls. Of the patients with celiac disease, 43% were positive for HLA B8, 85% for DR3, and 66% for DR7. Although lower, no difference was found in the expression of HLA B8, DR3, and DR7 in the Italian and German controls. The data presented here strongly suggest that there is little association between the incidence of the disease and HLA type in the two ethnic populations. However, from preliminary data, it is postulated that the age of the infant when gluten is added to its diet will affect the incidence of celiac disease.

Celiac Disease↗

Celiac disease and autoimmune endocrinologic disorders.

Patients with insulin-dependent diabetes mellitus, autoimmune thyroid disease, Addison's disease, and alopecia areata are at increased risk of celiac disease. We investigated whether patients with more than one autoimmune endocrinologic disorder are even more susceptible to celiac disease or have celiac-type mucosal inflammation. All 62 patients found to have such multiple diseases in 1994-1996 were investigated. Small bowel biopsy was performed on all voluntary nonceliac subjects. The villous structure and density of intraepithelial lymphocytes were examined, and HLA-DQ alleles were determined. Seven (11%) patients had celiac disease: six cases were detected earlier and there was one new case; in addition, two had minor villous deterioration and five an increased density of mucosal intraepithelial gammadelta+ T-cells. HLA-DQ2 or DQ8 alleles were found in all subjects with mucosal changes. Patients with multiple autoimmune disorders clearly run an increased risk of developing celiac disease, and some of them have minor mucosal changes compatible with the early signs of the disease.

Addison Disease↗

Effectiveness of antigliadin antibodies as a screening test for celiac disease in children.

OBJECTIVE: To test the effectiveness of serologic antigliadin antibody (AGA) testing in predicting celiac disease in children. DESIGN: Prospective clinical assessment. SETTING: Hôpital Sainte-Justine, montreal. PATIENTS: A total of 176 children with possible celiac disease who were referred for duodenal biopsy between January 1992 and June 1995. OUTCOME MEASURES: IgA and IgG AGA titres, as determined by enzyme-linked immunosorbent assay (ELISA); duodenal biopsy; clinical outcome on a gluten-free diet. RESULTS: Of the 176 children 30 were found to have celiac disease according to the criteria of the European Society of Pediatric Gastroenterology and Nutrition (ESPGAN). The sensitivity and specificity of the IgA AGA titre, as well as its positive and negative predictive values, were 80%, 92%, 67% and 96% respectively; the corresponding values for the IgG AGA titre were 83%, 79%, 45% and 96%. The respective values for IgA and IgG AGA titres combined were 93%, 71%, 43% and 98%. Only 2 of the 30 patients with celiac disease had false-negative results for both IgA and IgG AGA titres. The IgA and IgG AGA titres decreased significantly (p < 0.005) in all 11 patients after being on a gluten-free diet for at least 10 months and reached normal values in 8. CONCLUSION: AGA screening for celiac disease permits better selection of patients for duodenal biopsy and adds specificity to the histologic diagnosis. Such screening cannot replace intestinal biopsy, which remains the gold standard for diagnosis.

Adolescent↗

Prevalence of celiac disease in Argentina: screening of an adult population in the La Plata area.

OBJECTIVES: Up to now, the epidemiological characteristic of celiac disease among adults in South America remains unknown. The present prospective screening was designed to determine the prevalence of celiac disease in adults from the general population in an urban area of Argentina. METHODS: Between January. 1998, and May, 2000, all couples attending a centralized laboratory for an obligatory prenuptial examination in the La Plata area were offered participation in a screening program for celiac disease. The study included 2000 subjects (996 women; median age 29 yr, range 16-79 yr). All individuals completed a clinical questionnaire at the time that serum samples were obtained. A three-step screening protocol was used, as follows: 1) all samples were tested for antigliadin antibodies (AGAs) (type IgA and IgG); 2) samples that were IgA AGA positive were tested for antiendomysial antibody (EmA type IgA); samples that were positive for AGA-G but negative for IgA AGAs were tested for total IgA serum levels and EmA type IgG; and 3) subjects who were EmA-positive were referred for intestinal biopsy. RESULTS: At the end of the screening we detected 10 subjects who were EmA-A positive and two others who were IgA-deficient (both were EmA-G positive). Up to now, 11 of the 12 subjects (including nine EmA-positive and two IgA-deficient subjects) had endoscopic intestinal biopsies showing the characteristic celiac histology. The remaining EmA-positive individual was considered to be affected by celiac disease. The overall prevalence assessed was 1:167 (6.0 x 1000 subjects; 95% CI = 3.1-10.5). Eight of the 12 (67%) subjects were female (1:124; 8.0 x 1000; 95% CI = 3.5-15.8) and four (33%) were male (1:251; 4.0 x 1000; 95% Cl = 1.1-10.2). Although eight new patients were considered to be asymptomatic, three presented with a subclinical course and one was classically symptomatic. Only one patient had been previously diagnosed with celiac disease. CONCLUSIONS: Our screening protocol showed a very high prevalence of celiac disease for an urban area of Argentina that is ethnically similar to 90% of the general population of the country. The prevalence among women was double that for men, and the heterogeneous clinical picture of new patients showed predominance of asymptomatic cases.

Adolescent↗

Prostaglandins in small intestinal mucosa of children with celiac disease.

Diarrhea is one of the important clinical symptoms in patients suffering from celiac disease and is attributed mainly to malabsorption. We determined prostanoid content in small intestinal mucosa of five patients with active celiac disease and in a control group consisting of six patients. Prostaglandin E2 and thromboxane B2 content in duodenal mucosa of patients with active celiac disease was 1,581 +/- 161 and 118 +/- 40 pg/mg wet wt, respectively, significantly higher than their content in duodenal mucosa of the control group, 378 +/- 86 and 8 +/- 8, p less than 0.001 and p less than 0.02, respectively. 6-Ketoprostaglandin F1 alpha content in celiac patients was not significantly different from its content in the control group: 908 +/- 437 and 124 +/- 53 pg/mg wet wt, respectively. It is possible that, in celiac disease, increased mucosal prostanoid content may contribute, at least in part, to intestinal electrolyte and fluid secretion and consequent diarrhea.

6-Ketoprostaglandin F1 alpha↗

[Convulsive disorder in celiac disease].

Several recent reports have described convulsions in patients with celiac disease, and in some, folic acid deficiency and brain calcifications. A 40-year-old woman with celiac disease, hypocalcemia and generalized tonic-clonic seizures is reported. Hypocalcemia was corrected and convulsions disappeared, but the EEG showed persistent occipital epileptiform activity. Patients with celiac disease and hypocalcemia due to malabsorption are particularly at increased risk for convulsions. Therefore, even a mild degree of hypocalcemia in these patients should be corrected as soon as possible.

Adult↗