Characteristics of Anemia in Celiac Disease

Study Overview
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Brief Summary
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Celiac Disease (CD) is an autoimmune disease involving the mucosa of the small intestine, triggered by the ingestion of gluten in genetically predisposed individuals. CD represents a global health problem. The clinical presentation of CD is characterized by a broad spectrum of both intestinal and extraintestinal manifestations, involving one or more organs. Anemia is one of the most common extraintestinal clinical manifestations of CD, present in more than half of adult patients at the time of diagnosis. Anemia in CD has a multifactorial pathogenesis: a) lack of absorption (or, sometimes, loss, as in the case of iron), of some micronutrients, such as iron, folate, vitamin B12, copper and zinc, b) coexistence of a chronic inflammatory state, as in the case of inflammatory bowel disease (IBD), c) refractory CD, d) medullary aplasia. The main purpose of this multicentre research is to evaluate, retrospectively, analyzing the clinical and laboratory data of CD patients, the presence, prevalence, severity, and morphological characteristics of anemia, trying to define, when possible, the underlying pathogenetic mechanisms, paying particular attention to the characteristics of menstrual cycles, the iron, folate and vitamin B12 metabolism, any chronic inflammatory state, and thyroid hormones. It will be also recorded, in a subgroup of the selected CD patients, any therapeutic responses (i.e., improvement/regression) of anemia after at least one year of GFD.

Detailed Description
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Celiac Disease (CD) is an autoimmune disease involving the mucosa of the small intestine, triggered by the ingestion of gluten in genetically predisposed individuals. CD represents a global health problem. The prevalence of CD, confirmed by intestinal biopsy, is estimated to be over 1% of the population of the Western world. Interestingly, the incidence of CD is continuously increasing around the world. CD is more common in women and children, although it is also becoming a common diagnosis also in men and adults. The clinical presentation of CD is characterized by a broad spectrum of both intestinal and extraintestinal manifestations, involving one or more organs. Several clinical categories of CD have been identified, including classical/typical CD (characterized by intestinal symptoms), atypical/subclinical CD (characterized by minor or extraintestinal symptoms), and silent CD (characterized by no symptoms). The category of potential CD was established for those patients with positive serology but without crypt hyperplasia and villous atrophy on duodenal biopsy. Duodenal biopsies can be avoided in the pediatric population, with high positive titer of IgA class anti-tTG (>10 times the upper limit of normal), associated with EMA-positivity. The treatment of CD is based on gluten-free diet (GFD). Anemia is one of the most common extraintestinal clinical manifestations of CD, present in more than half of adult patients at the time of diagnosis. Anemia in CD has a multifactorial pathogenesis: a) lack of absorption (or, sometimes, loss, as in the case of iron), of some micronutrients, such as iron, folate, vitamin B12, copper and zinc, b) coexistence of a chronic inflammatory state, as in the case of inflammatory bowel disease (IBD), c) refractory CD, d) medullary aplasia. The main purpose of this multicentre research is to evaluate, retrospectively, analyzing the clinical and laboratory data of CD patients, the presence, prevalence, severity, and morphological characteristics of anemia, trying to define, when possible, the underlying pathogenetic mechanisms, paying particular attention to the characteristics of menstrual cycles, the iron, folate and vitamin B12 metabolism, any chronic inflammatory state, and thyroid hormones. It will be also recorded, in a subgroup of the selected CD patients, any therapeutic responses (i.e., improvement/regression) of anemia after at least one year of GFD.

Official Title
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Clinical Characteristics and Pathogenic Mechanisms of Anemia in Celiac Disease

Conditions
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Celiac Disease

Intervention / Treatment
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* Other: Presence, prevalence, severity, and morphological characteristics of anemia
* Other: Effect of gluten-free diet on anemia


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: CD will be diagnosed according to the current guidelines. In details, the following standard criteria will be adopted to diagnose CD (4 out of 5 rule): gluten/wheat-dependent symptoms, both intestinal and extraintestinal positivity of anti-deamidated gluten peptides (DPG) IgA and IgG antibodies, anti-transglutainase (tTG) IgA and IgG antibodies, and endomysium antibodies (EMA) presence of crypt hyperplasia and duodenal villous atrophy on duodenal biopsy presence of HLA haplotypes DQ2 and/or DQ8 resolution of symptoms with a rigorous GFD Additional inclusion criteria, both for the retrospective and prospective part of the study, will be: age >18 and <65 years complete clinical records clinical and laboratory follow-up of at least one year from diagnosis - Exclusion Criteria: age <18 and >65 years incomplete medical records lack of clinical and laboratory follow-up of at least one year from diagnosis pregnancy alcohol and/or drug abuse diagnosis of IBD or other gastrointestinal organic disease

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Other: Presence, prevalence, severity, and morphological characteristics of anemia|Evaluation of the presence, prevalence, severity, and morphological characteristics of anemia, trying to define, when possible, the underlying pathogenetic mechanisms, paying particular attention to the characteristics of menstrual cycles, the iron, folate and vitamin B12 metabolism, any chronic inflammatory state, and thyroid hormones.|
|Other: Effect of gluten-free diet on anemia|Evaluation of the therapeutic responses (i.e., improvement/regression) of anemia after at least one year of GFD.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Presence, severity and morphologic characteristic of anemia | Blood count to evaluate red cell count and morphology | At baseline (=before diagnosis, on a gluten-containing diet) and at follow-up (=after at least one year of GFD) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathogenic mechanisms of anemia | Evaluation of inadequate production or loss of erythrocytes a a result of bleeding or hemolysis | At baseline (=before diagnosis, on a gluten-containing diet) and at follow-up (=after at least one year of GFD) |