Characteristics of Anemia in Celiac Disease

Clinical Characteristics and Pathogenic Mechanisms of Anemia in Celiac Disease

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.

Study Overview

• Status: Completed
• Conditions: Celiac Disease
• Intervention / Treatment: Other: Presence, prevalence, severity, and morphological characteristics of anemia; Other: Effect of gluten-free diet on anemia

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 159

Contacts and Locations

Study Locations

• Italy
  • Palermo, Italy, 90129
    • Department of Internal Medicine, University Hospital of Palermo
  • Agrigento
    • Sciacca, Agrigento, Italy, 92019
      • Department of Internal Medicine, Giovanni Paolo II Hospital of Sciacca
  • PA
    • Palermo, PA, Italy, 90146
      • Internal Medicine Division of the "Cervello-Villa Sofia" Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

We will enroll CD patients.

Description

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

Study Plan

How is the study designed?

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: University of Palermo
• Investigators: Study Director: Antonio Carroccio, MD, University of Palermo

Publications and helpful links

General Publications

• Montoro-Huguet MA, Santolaria-Piedrafita S, Canamares-Orbis P, Garcia-Erce JA. Iron Deficiency in Celiac Disease: Prevalence, Health Impact, and Clinical Management. Nutrients. 2021 Sep 28;13(10):3437. doi: 10.3390/nu13103437.
• Martin-Masot R, Nestares MT, Diaz-Castro J, Lopez-Aliaga I, Alferez MJM, Moreno-Fernandez J, Maldonado J. Multifactorial Etiology of Anemia in Celiac Disease and Effect of Gluten-Free Diet: A Comprehensive Review. Nutrients. 2019 Oct 23;11(11):2557. doi: 10.3390/nu11112557.
• Elli L, Norsa L, Zullo A, Carroccio A, Girelli C, Oliva S, Romano C, Leandro G, Bellini M, Marmo R, Soncini M, Monica F, De Francesco V, Paulon E, Cappellini MD, Motta I, Ferretti F, Orlando S, Mansueto P, Buscarini E, Manfredi G, Agostoni C, Tomba C, Cannizzaro R. Diagnosis of chronic anaemia in gastrointestinal disorders: A guideline by the Italian Association of Hospital Gastroenterologists and Endoscopists (AIGO) and the Italian Society of Paediatric Gastroenterology Hepatology and Nutrition (SIGENP). Dig Liver Dis. 2019 Apr;51(4):471-483. doi: 10.1016/j.dld.2019.01.022. Epub 2019 Feb 11.
• Stefanelli G, Viscido A, Longo S, Magistroni M, Latella G. Persistent Iron Deficiency Anemia in Patients with Celiac Disease Despite a Gluten-Free Diet. Nutrients. 2020 Jul 22;12(8):2176. doi: 10.3390/nu12082176.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2001
• Primary Completion (Actual): January 1, 2020
• Study Completion (Actual): July 31, 2021

Study Registration Dates

• First Submitted: November 30, 2021
• First Submitted That Met QC Criteria: December 11, 2021
• First Posted (Actual): December 29, 2021

Study Record Updates

• Last Update Posted (Actual): December 29, 2021
• Last Update Submitted That Met QC Criteria: December 11, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Metabolic Diseases; Gastrointestinal Diseases; Intestinal Diseases; Malabsorption Syndromes; Celiac Disease
• Other Study ID Numbers: ACPM28

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No