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PubMed2003

Additional factor in some HLA DR3/DQ2 haplotypes confers a fourfold increased genetic risk of celiac disease.

Although HLA-DQ genes are the major celiac disease (CD) susceptibility genes, results from Finnish families suggest that not all DQ2-encoding haplotypes confer equal susceptibility to CD, implying the effect of other gene(s) in the HLA region. The aim of the present work was to extend and confirm the aforementioned results in a southern European population ( Italian) and to better localize the additional risk factor/s. The association of nine loci spanning the HLA region from DR to HFE, 4.5-Mb telomeric of HLA-A, was tested. The analysis was performed by comparing marker frequencies in DR3-DQ2 haplotypes transmitted and non-transmitted to the affected offspring in 156 Italian CD families selected for having at least one DR3-positive parent. The same analysis was performed independently in 101 Finnish CD families selected with the same criteria. Three alleles, MICA-A5.1, MICB-CA24 and MIB-350, all characteristic of the B8-DR3 extended haplotype, showed a significantly increased frequency in DR3 transmitted haplotypes in the Italian families. DR3 haplotypes carrying the combination of these alleles conferred an approximate fourfold increased CD risk. B8-DR3 transmitted haplotypes were significantly more conserved telomerically down to the MIC-Class I region. Similar results were seen in the Finnish families. The major conclusion that holds true in both populations is that, while DQ2 is an absolute requirement for the development of CD, the presence of an additional genetic factor within the MIC-Class I region confers an approximate 4-fold increased risk of the disease.

Celiac Disease↗
PubMed1999

Linear growth and skeletal maturation in subjects with treated celiac disease.

BACKGROUND: The aim of this study was to report on the long-term growth and development in a group of treated patients with celiac disease. METHODS: The study includes 26 patients (11 boys and 15 girls) with typical celiac disease who were younger than 2.5 at diagnosis and were followed by means of a growth longitudinal monitoring from the introduction of a gluten-free diet (mean age, 1.7 +/- 0.5 years) until adulthood, over a median period of 15.3 years. Growth indicators used were: height, skeletal age, weight and BMI. RESULTS: At the time of admission, the patients had a general tendency to short stature, underweight and retarded skeletal maturation. They did not catch up completely in height and skeletal age after a dietary treatment period of 3 years. Most of them were seen to be slightly below average height for age during childhood and adolescence with skeletal maturity retardation, even if a fairly large interindividual variation of height profiles was evident. CONCLUSIONS: Notwithstanding the early treatment, the careful follow-up, and the good adhesion to the dietary rules of the patients under study, slight negative effects of the disease on growth were not avoided.

Body Height↗
PubMed1999

Sensitivity of antiendomysium and antigliadin antibodies in untreated celiac disease: disappointing in clinical practice.

OBJECTIVE: We have undertaken a study to assess the efficiency of serological tests in the diagnosis of celiac disease (CD) during the period January 1, 1994 to January 7, 1997. Our aim was to evaluate the sensitivity of IgA antiendomysium (EMA) and IgA antigliadin (AGA) with regard to the degree of histological abnormality in biopsy specimens of small intestine in untreated celiac disease patients and first-degree relatives. METHODS: The study population comprised 101 cases: 85 untreated celiac patients and 16 first-degree relatives with a mean age of 42 yr (range, 2-76 yrs). Sixteen of 85 were excluded from study because they did not satisfy the study or diagnostic criteria of CD. EMA and AGA have been compared with the degree of villous atrophy (VA) in 69 celiac patients and 16 relatives according to the Marsh criteria of 1992. We divided the Marsh III histology into three subgroups as follows: Marsh IIIa (partial VA), Marsh IIIb (subtotal VA), and Marsh IIIc (total villous atrophy). RESULTS: The specificity and positive predictive value of EMA for CD was excellent, because all EMA-positive patients (n = 42) were diagnosed with CD. The sensitivity of EMA, however, differed between CD subgroups; in patients with total VA, the sensitivity of EMA was 100% (17/17). However, in patients with partial VA (Marsh IIIa), the sensitivity of EMA was disappointing, only 9/29 (31%). Three of 72 celiacs with Marsh IIIb and Marsh IIIc had IgA deficiency and were excluded from the study. Elevated AGA has been detected in the sera of 39 of 69 (62%) patients. A combination of EMA and AGA tests showed a sensitivity of 76% (53/69). None of 16 first-degree relatives with Marsh I-II had positive EMA. CONCLUSIONS: Interpretation of negative serology needs great awareness. Although EMA sensitivity in total villous atrophy is excellent, in partial villous atrophy the sensitivity of EMA appears to be disappointing. Our experience shows that EMA and AGA have only limited value in screening programs for CD.

Adult↗
PubMed1998

Thyroid and celiac disease: clinical, serological, and echographic study.

OBJECTIVE: We sought to reevaluate the prevalence of thyroid dysfunction and thyroid autoimmunity in 47 patients with celiac disease; 91 healthy subjects were studied as controls. Both patients and controls were from Sardinia, Italy. METHODS: Diagnosis of celiac disease was made on the basis of clinical history, presence of positive antigliadin IgA (AGA-A) and IgG (AGA-G) antibodies, antireticulin antibodies (ARA), antiendomysium antibodies (EMA), and was confirmed by jejunal biopsy. HLA class II typing for DQB1 and DQA1 alleles was performed in 36/47 celiac patients. Thyroid was evaluated by palpation and echography; serum free thyroid hormones (FT4, FT3), thyrotropic hormone (TSH), and antithyroid peroxidase autoantibodies (anti-TPO) were assayed by radioimmunoassays. RESULTS: The prevalence of anti-TPO was higher in celiac patients (29.7%) than in healthy controls (9.6%) (p < 0.001) and thyroid echography frequently displayed (42.5%) a hypoechogenic pattern. Five anti-TPO-positive celiac patients were hypothyroid (two overt, three subclinical). A higher but not significantly different prevalence of anti-TPO (3/7 = 42.8%) was found in celiac patients displaying the DQB1*0502 genotype, when compared with the remaining patients (8/29 = 27.6%). CONCLUSIONS: An elevated prevalence of clinical and subclinical autoimmune thyroid autoimmunity was found in Sardinian celiac patients, especially in those displaying the DQB1*0502 genotype; this finding could be related to a particular genetic background of the Sardinian population.

Adult↗
PubMedDate not supplied

Malt lymphoma as first clinical presentation of a celiac disease.

We report a case of a 35 year-old-woman who suffered from abdominal pain and weight loss. Asymptomatic celiac disease was discovered and complicated with a MALT Lymphoma in the jejunum. This is an uncommon combination because lymphoma that arises in the presence of enteropathy is commonly from T lymphocytes. Also because it normally appears in patients with long standing celiac disease who report a recrudescence of the abdominal symptoms.

Adult↗
PubMed1999

A prevalence study of celiac disease in persons with Down syndrome residing in the United States of America.

In order to estimate the prevalence of celiac disease in persons with Down syndrome, 105 patients with this chromosomal disorder residing on the East Coast of the United States of America were enrolled in this study. IgA and IgG antigliadin antibodies (AGA) were determined using a fluorescent immunoenzymatic assay, and antiendomysium antibodies (AEA) were measured with immunofluorescence on monkey oesophagus. Of the 105 patients, 5 were positive for AEA, 4 were positive for IgG AGA, and 1 was positive for IgG AGA and AEA. Of the five patients with high titres of AEA, four consented to a jejunal biopsy, which revealed significant villous atrophy. Thus, 4 (possibly 5) patients in this cohort of 105 individuals with Down syndrome have celiac disease.

Adolescent↗
PubMed2006

Nutritional management of the gluten-free diet in young people with celiac disease in The Netherlands.

BACKGROUND: For young people with celiac disease, adherence to the gluten-free diet may be difficult to achieve and gluten restriction may lead to insufficient nutrient intake and unbalanced food intake resulting in overweight. In The Netherlands, no nutritional information is available. Therefore, we evaluated the nutritional management and nutritional state in young celiac patients. METHODS: The Dutch Celiac Society invited all its members aged 12 to 25 years to complete a food record and a questionnaire. Nutrient intakes were compared with the recommendations and the intake in the general population. Total immunoglobin A, endomysial antibody, tissue transglutaminase and IgA gliadin were determined, and height and weight were assessed. RESULTS: Strict dietary compliance was reported by 75%. The fiber and iron intakes were significantly lower, and the saturated fat intake significantly higher than recommended but comparable with the general population. Most of the patients (61%) found the diet easy to follow. Regular medical controls were reported by 86% but regular dietary controls by only 7% of the patients. Mean and SD scores for height and body mass index were -0.3 +/- 1.1 and -0.3 +/- 0.8, respectively. CONCLUSIONS: The dietary compliance in this group is high, the nutritional state is adequate, but the nutrient intake is not. Better medical and dietary support is necessary to prevent long-term complications and to achieve an ongoing satisfying management in this group of young patients with a chronic disorder.

Adolescent↗
PubMed2001

Celiac disease and its link to type 1 diabetes mellitus.

Celiac disease (CD) is a small intestinal disorder with overt malabsorption in the minority and with subclinical or atypical symptoms in the majority of patients. It is triggered by gluten and related cereal proteins in a unique genetic background (HLA-DQ2 or DQ8 and other unmapped genes). CD is characterized by a highly specific mucosal autoantibody response to tissue transglutaminase. In the intestine this enzyme creates antigenic neoepitopes in gluten peptides which are more efficiently presented to the immune system in the context of HLA-DQ2 or DQ8. Between 3% and 6% of patients with type 1 diabetes mellitus (DM) have (atypical) CD, and the prevalence of a variety of autoimmune diseases in patients with CD correlates with the time of gluten exposure, reaching 35% after 20 years. It is still unknown whether oligosymptomatic CD favors the development of type 1 DM and whether a gluten-free diet modifies the progression of DM in general. Apart from shared or adjacent HLA loci in both diseases, post-translational modification of potential autoantigens by enzymes such as tissue transglutaminase could play a role in the autoimmunity of type 1 DM.

Autoantigens↗
PubMed1997

Longitudinal study on the effect of treatment on body composition and anthropometry of celiac disease patients.

OBJECTIVES: This prospective study was designed to assess the nutritional changes associated with the long-term treatment of celiac disease. In addition, we analyzed whether these changes were related to the degree of compliance with a gluten-free diet. METHODS: We studied nutritional parameters and body composition in 25 newly diagnosed celiac patients after a mean period of 37 months (range 25-49 months) on a gluten-free diet. Body composition parameters (fat, lean tissue, and bone masses) were measured by dual energy x-ray absorptiometry. Anthropometry was measured according to conventional formulas. RESULTS: At diagnosis, fat (-49%), lean tissue (-12%), and bone (-24%) compartments were reduced, compared with that of sex- and age-matched controls. After treatment, we noted a significant increase in body weight (p < 0.0001), fat mass (p < 0.0005), bone mass (p < 0.002), and body mass index (p < 0.005). In contrast, we did not observe a significant increase in lean-tissue mass or muscle mass. Patients who adhered strictly to a gluten-free diet experienced a greater, though nonsignificant improvement in fat mass, body weight, and body mass index than patients whose compliance had been partial. Mean caloric intake at the end of the study was significantly lower among those patients who had adhered strictly to a gluten-free diet, compared with those who had complied only partially with the diet (p < 0.05). CONCLUSIONS: This study shows that the institution of a gluten-free diet in celiac disease patients results in a significant improvement in nutritional parameters, as measured by anthropometry and/or body composition. This effect was more pronounced in patients who followed strict gluten restriction and was related mainly to changes in fat and bone compartments.

Adult↗
PubMed2006

The role of ultrasonography in patients with celiac disease.

The aim of the present review was to summarize the current evidence on the role of ultrasonography (US) and doppler-US in the diagnosis of celiac disease. Several ultrasonographic signs have been reported in the association with celiac disease in studies using real-time US. Firstly, case control studies identified some of these US signs and then in a prospective series some of these parameters, due to their high specificity, have been shown to be of value in confirming CD diagnosis, whereas others, due to their high sensitivity, have been demonstrated to be useful in excluding the presence of the disease. The pattern of splanchnic circulation in CD have extensively been investigated by several studies all of which reported similar results and identified a hyperdynamic mesenteric circulation that reverts to normal values after successful a gluten-free regimen. The last part of this review will deal with the possible role of US in identifying the most severe and common intestinal complication of CD, i.e. the enteropathy-associated T cell non-Hodgkin lymphoma.

Abdomen↗
PubMed2003

Recognizing and managing celiac disease in primary care.

PURPOSE: To heighten the awareness of primary care clinicians regarding the prevalence, clinical manifestations, diagnosis, and treatment of celiac disease (CD) in the primary care setting. DATA SOURCES: Selected research, clinical guidelines, research and clinically based articles from current scientific literature, and current medical textbooks. CONCLUSIONS: Celiac disease is commonly under diagnosed or misdiagnosed. Until recently, it was considered rare in the United States. New data indicate that 1:150 Americans are affected and demonstrate the protective effects of early diagnosis and treatment. IMPLICATIONS FOR PRACTICE: Delays in the diagnosis and treatment of CD increase the risk of early mortality, associated autoimmune disease, neurologic complications, gastrointestinal malignancy, and fetal growth retardation, where pregnancy precedes diagnosis. Primary care clinicians must cultivate a high index of suspicion for CD in the primary care setting and bear it in mind as a differential diagnosis in many clinical situations.

Adult↗
PubMed2006

[Celiac disease revealed by hypocalcemia complicating total thyroidectomy: a case report].

In order to illustrate a particular circumstance of diagnosis of celiac disease, we report the case of 54-year-old women with a history of thyroid enlargement with normal thyroid function and positive anti-peroxidase antibodies. Immediately after total thyroidectomy with preservation of the parathyroid glands, she developed tetany with total serum calcium level at 50mg/l. Intravenous calcium infusion increased the calcium level and led to resolution of hypocalcemia-induced signs but there was no result when calcium and vitamin D were taken orally. The diagnosis of malabsorption was very probable in light of the family history of celiac disease, the anemia and the hypoalbuminemia. The diagnosis was confirmed by antibodies assay and endoscopy. The PTH level was less than 1 pg/l and radiography showed signs of hyperparathyroidism. Gluten-free diet, calcium and vitamin D led to an improvement of serum calcium.

Celiac Disease↗
PubMed2002

Serum soluble interleukin-2 receptor, interleukin-6, and tumor necrosis factor-alpha levels in children with celiac disease: response to treatment.

OBJECTIVES: T-cell mediated immune response to dietary gluten and cytokines release are important for the enteropathy seen in celiac disease. We investigated the serum levels of soluble interleukin-2 receptor, interleukin-6, and tumor necrosis factor-alpha in celiac children before and after gluten exclusion. METHODS: Cytokine levels were determined using enzyme immunoassay in serum from 12 untreated celiac patients, 16 treated celiac patients on a gluten-free diet for at least two years, and from 26 control children. Eight of 12 untreated patients were also investigated at 6 and 12 months after gluten exclusion. Serum IgA antiendomysium antibodies were also assayed by indirect immunofluorescence. RESULTS: Soluble interleukin-2 receptor and interleukin-6 levels were significantly increased in untreated celiac patients compared with treated and control children. There was no difference in the tumor necrosis factor-alpha levels between the groups. Soluble interleukin-2 receptor levels were the only ones significantly decreased at 12 months after gluten exclusion. However, soluble interleukin-2 receptor and interleukin-6 levels at 12 months were significantly higher compared with controls. Antiendomysium antibodies had a diagnostic sensitivity of 100% and the titers decreased significantly after 12 months of gluten exclusion. A significant positive correlation was found between antiendomysium antibody titers with both soluble interleukin-2 receptor and interleukin-6 values. CONCLUSIONS: The serum soluble interleukin-2 receptor and interleukin-6 levels may be used as a noninvasive measure of celiac disease activity and response to treatment.

Adolescent↗
PubMed1992

Acute onset of celiac disease in the puerperium.

An acute, severe onset of celiac disease is very unusual in adults. We describe its occurrence postpartum in two patients. These, together with two similar cases previously reported, suggest a causal association with the puerperium. Possible causes include potentiation of a pathogenetic immune reaction and hormonal mechanisms.

Adult↗
PubMed2006

[Reproduction, endocrine disorders and celiac disease: risk factors of osteoporosis].

In genetically predisposed individuals, celiac disease (CD) is permanent intolerance to gluten. Besides the overt enteropathy, there are clinical and subclinical forms which appear later in life; target organs include liver, thyroid, skin and reproductive systems. CD interference is related to the different concurrent genetic-environmental factors, showing multifactorial nature. CD induces malabsorption with consequent deficiencies of micronutrients essential for organogenesis, spermatogenesis and bone structure, such as vitamin D and calcium. In fact, among extraintestinal manifestations of CD, osteoporosis deserves attention because it can be a sign of silent CD. In celiac patients' serum, cytochinic imbalance related to bone loss is present; in vitro these sera act on the osteoblastic activity. The IL-1b is also present in celiac patients' relatives, confirming the genetic predisposition to its etiopathogenesis which is also regulated by endocrine-environmental factors. In females, CD acts indirectly on the bone, determining early menopause and amenorrhea. Even frequent pregnancies and long periods of lactation can bring to bone loss; in such periods, silent CD can appear, suggesting the presence of endocrine-immunology factors. In celiac males, osteoporosis presence, besides calcium and vitamin D deficiencies, is associated to growth hormone deficit and hypogonadism, which is related to hyperprolactinemia, endocrine factors which affect the reproduction. Osteoporosis is relevant among the elderly and vitamin D and calcium supplementations are important to people diagnosed with CD later in life. Thus, to prevent damages such as osteoporosis, early CD screening among people with reproductive problems is necessary.

Celiac Disease↗
PubMed1990

Anemia: monosymptomatic celiac disease. A report of 3 cases.

Patients with monosymptomatic celiac disease (CD) can escape diagnosis for a long period. Anemia is a common finding in CD, although anemia as the sole symptom is relatively unknown. We report on three patients who presented with iron deficiency anemia and no other symptom, in whom CD was considered and diagnosed several to many years after the anemia was documented.

Anemia, Hypochromic↗
PubMed2003

Prevalence of celiac disease in at-risk and not-at-risk groups in the United States: a large multicenter study.

BACKGROUND: Celiac disease (CD) is an immune-mediated enteropathic condition triggered in genetically susceptible individuals by the ingestion of gluten. Although common in Europe, CD is thought to be rare in the United States, where there are no large epidemiologic studies of its prevalence. The aim of this study was to determine the prevalence of CD in at-risk and not-at-risk groups in the United States. METHODS: Serum antigliadin antibodies and anti-endomysial antibodies (EMA) were measured. In EMA-positive subjects, human tissue transglutaminase IgA antibodies and CD-associated human leukocyte antigen DQ2/DQ8 haplotypes were determined. Intestinal biopsy was recommended and performed whenever possible for all EMA-positive subjects. A total of 13 145 subjects were screened: 4508 first-degree and 1275 second-degree relatives of patients with biopsy-proven CD, 3236 symptomatic patients (with either gastrointestinal symptoms or a disorder associated with CD), and 4126 not-at-risk individuals. RESULTS: In at-risk groups, the prevalence of CD was 1:22 in first-degree relatives, 1:39 in second-degree relatives, and 1:56 in symptomatic patients. The overall prevalence of CD in not-at-risk groups was 1:133. All the EMA-positive subjects who underwent intestinal biopsy had lesions consistent with CD. CONCLUSIONS: Our results suggest that CD occurs frequently not only in patients with gastrointestinal symptoms, but also in first- and second-degree relatives and patients with numerous common disorders even in the absence of gastrointestinal symptoms. The prevalence of CD in symptomatic patients and not-at-risk subjects was similar to that reported in Europe. Celiac disease appears to be a more common but neglected disorder than has generally been recognized in the United States.

Adolescent↗